Sustiva

• Sustiva^®

Before taking efavirenz, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: mental/mood conditions (such as depression, thoughts of suicide, psychosis), liver problems (such as hepatitis B or C, cirrhosis), drug/substance/alcohol abuse, seizures, high cholesterol/triglyceride levels.This drug may make you dizzy or drowsy or cause trouble concentrating. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.A rash may be more common and serious in children taking efavirenz. Report any rash immediately. The doctor may prescribe an antihistamine for your child to take before efavirenz is started. Consult the doctor for more information.This medication is not recommended for use during pregnancy. It may harm an unborn baby, especially if taken during the first 3 months of pregnancy. Women of childbearing age should have a pregnancy test before starting efavirenz. It is important to prevent pregnancy while taking this medication and for 3 months after treatment. Consult your doctor about using at least 2 reliable forms of birth control (such as condoms with birth control pills) during treatment and for 3 months after the end of treatment (see also Drug Interactions section). If you become pregnant or think you may be pregnant, tell your doctor immediately. Discuss the risks and benefits of HIV treatment and alternatives to efavirenz during pregnancy to decrease the risk of HIV transmission to the baby.It is not known if efavirenz passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.

Efavirenz may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Drinking alcohol can increase certain side effects of efavirenz.

Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

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

If Sustiva 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.

Sustiva does not cure HIV or AIDS. People taking Sustiva may still develop other infections and complications. Therefore, it is very important that you stay under the care of your doctor.

Sustiva has not been shown to reduce the risk of passing HIV to others. Therefore, continue to practice safe sex, and do not use or share dirty needles.

• Keep Sustiva at room temperature (77° F) in the bottle given to you by your pharmacist. The temperature can range from 59° to 86° F.
• Keep Sustiva out of the reach of children.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• a seizure (convulsions);

• liver problems--nausea, upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, redness or burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Efavirenz may cause serious psychiatric symptoms including confusion, severe depression (feeling sad or hopeless), suicidal thoughts, anxiety, paranoia, hallucinations, trouble speaking or moving, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.

Efavirenz may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with efavirenz. Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

• cold sores, sores on your genital or anal area;

• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

• trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects may include:

• nausea, vomiting;

• dizziness, drowsiness, trouble concentrating;

• mild skin rash;

• headache, tired feeling;

• sleep problems (insomnia), strange dreams; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

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.

• Pharmacologically related to other NNRTIs (e.g., delavirdine, etravirine, nevirapine, rilpivirine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretrovirals.1 2 3 6 12 14 52 53 212 215

• Active against HIV-1; inactive against HIV-2.1 3

• Inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase.1 3

• HIV-1 with reduced susceptibility to efavirenz have been selected in vitro and have emerged during therapy with the drug.1 3 9 14 18 18

• Strains of HIV-1 resistant to efavirenz may be cross-resistant to some other NNRTIs (e.g., delavirdine, nevirapine).3 9 10 18 32 50 200 201 1 215

• Cross-resistance between efavirenz and NRTIs unlikely since the drugs bind at difference sites on reverse transcriptase and have difference mechanisms of action.1 3 9 10 32 Cross-resistance between efavirenz and PIs unlikely since the drugs have different target enzymes and mechanisms of action.1 32

Drug Interactions

Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Likewise, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or CYP2B6. The most prominent effect of efavirenz at steady-state is induction of CYP3A and CYP2B6 [see Dosage and Administration (2.1) and Drug Interactions (7.1)].

QTc Prolongation

QTc prolongation has been observed with the use of efavirenz [see Drug Interactions (7.3,7.4) and Clinical Pharmacology (12.2)]. Consider alternatives to Sustiva when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.

Resistance

Sustiva must not be used as a single agent to treat HIV-1 infection or added on as a sole agent to a failing regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy. The choice of new antiretroviral agents to be used in combination with efavirenz should take into consideration the potential for viral cross-resistance.

Coadministration with Related Products

Coadministration of Sustiva with ATRIPLA (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) is not recommended unless needed for dose adjustment (eg, with rifampin), since efavirenz is one of its active ingredients.

Psychiatric Symptoms

Serious psychiatric adverse experiences have been reported in patients treated with Sustiva. In controlled trials of 1008 patients treated with regimens containing Sustiva for a mean of 2.1 years and 635 patients treated with control regimens for a mean of 1.5 years, the frequency (regardless of causality) of specific serious psychiatric events among patients who received Sustiva or control regimens, respectively, were severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%). When psychiatric symptoms similar to those noted above were combined and evaluated as a group in a multifactorial analysis of data from Study 006, treatment with efavirenz was associated with an increase in the occurrence of these selected psychiatric symptoms. Other factors associated with an increase in the occurrence of these psychiatric symptoms were history of injection drug use, psychiatric history, and receipt of psychiatric medication at study entry; similar associations were observed in both the Sustiva and control treatment groups. In Study 006, onset of new serious psychiatric symptoms occurred throughout the study for both Sustiva-treated and control-treated patients. One percent of Sustiva-treated patients discontinued or interrupted treatment because of one or more of these selected psychiatric symptoms. There have also been occasional postmarketing reports of death by suicide, delusions, psychosis-like behavior and catatonia although a causal relationship to the use of Sustiva cannot be determined from these reports. Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of Sustiva, and if so, to determine whether the risks of continued therapy outweigh the benefits. [See Adverse Reactions (6.1).]

Nervous System Symptoms

Fifty-three percent (531/1008) of patients receiving Sustiva in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% (156/635) of patients receiving control regimens [see Adverse Reactions (6.1, Table 3)]. These symptoms included, but were not limited to, dizziness (28.1% of the 1008 patients), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%), and hallucinations (1.2%). These symptoms were severe in 2.0% of patients; and 2.1% of patients discontinued therapy as a result. These symptoms usually begin during the first or second day of therapy and generally resolve after the first 2-4 weeks of therapy. After 4 weeks of therapy, the prevalence of nervous system symptoms of at least moderate severity ranged from 5% to 9% in patients treated with regimens containing Sustiva and from 3% to 5% in patients treated with a control regimen. Patients should be informed that these common symptoms were likely to improve with continued therapy and were not predictive of subsequent onset of the less frequent psychiatric symptoms [see Warnings and Precautions (5.5)]. Dosing at bedtime may improve the tolerability of these nervous system symptoms [see Dosage and Administration (2)].

Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with Sustiva + zidovudine + lamivudine, Sustiva + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among Sustiva-treated patients were generally similar to those in the indinavir-containing control arm.

Patients receiving Sustiva should be alerted to the potential for additive central nervous system effects when Sustiva is used concomitantly with alcohol or psychoactive drugs.

Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.

Embryo-Fetal Toxicity

Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Advise females of reproductive potential who are receiving Sustiva to avoid pregnancy. [See Use in Specific Populations (8.1 and 8.3).]

Rash

In controlled clinical trials, 26% (266/1008) of adult patients treated with 600 mg Sustiva experienced new-onset skin rash compared with 17% (111/635) of those treated in control groups [see Adverse Reactions (6.1)]. Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1008) of patients treated with Sustiva. The incidence of Grade 4 rash (eg, erythema multiforme, Stevens-Johnson syndrome) in adult patients treated with Sustiva in all studies and expanded access was 0.1%. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with efavirenz (median time to onset of rash in adults was 11 days) and, in most patients continuing therapy with efavirenz, rash resolves within 1 month (median duration, 16 days). The discontinuation rate for rash in adult clinical trials was 1.7% (17/1008).

Rash was reported in 59 of 182 pediatric patients (32%) treated with Sustiva [see Adverse Reactions (6.2)]. Two pediatric patients experienced Grade 3 rash (confluent rash with fever, generalized rash), and four patients had Grade 4 rash (erythema multiforme). The median time to onset of rash in pediatric patients was 28 days (range 3-1642 days). Prophylaxis with appropriate antihistamines before initiating therapy with Sustiva in pediatric patients should be considered.

Sustiva can generally be reinitiated in patients interrupting therapy because of rash. Sustiva should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash. For patients who have had a life-threatening cutaneous reaction (eg, Stevens-Johnson syndrome), alternative therapy should be considered [see Contraindications (4.1)].

Hepatotoxicity

Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity [see Adverse Reactions (6.1) and Use in Specific Populations (8.6)]. A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic disease or other identifiable risk factors [see Adverse Reactions (6.2)]. Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. In patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range, the benefit of continued therapy with Sustiva needs to be weighed against the unknown risks of significant liver toxicity.

Convulsions

Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures [see Nonclinical Toxicology (13.2)]. Caution should be taken in any patient with a history of seizures. Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.1)].

Lipid Elevations

Treatment with Sustiva has resulted in increases in the concentration of total cholesterol and triglycerides [see Adverse Reactions (6.1)]. Cholesterol and triglyceride testing should be performed before initiating Sustiva therapy and at periodic intervals during therapy.

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Sustiva. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies in mice and rats were carried out with efavirenz. Mice were dosed with 0, 25, 75, 150, or 300 mg/kg/day for 2 years. Incidences of hepatocellular adenomas and carcinomas and pulmonary alveolar/bronchiolar adenomas were increased above background in females. No increases in tumor incidence above background were seen in males. There was no NOAEL in females established for this study because tumor findings occurred at all doses. AUC at the NOAEL (150 mg/kg) in the males was approximately 0.9 times that in humans at the recommended clinical dose. In the rat study, no increases in tumor incidence were observed at doses up to 100 mg/kg/day, for which AUCs were 0.1 (males) or 0.2 (females) times those in humans at the recommended clinical dose.

Mutagenesis

Efavirenz tested negative in a battery of in vitro and in vivo genotoxicity assays. These included bacterial mutation assays in S. typhimurium and E. coli, mammalian mutation assays in Chinese hamster ovary cells, chromosome aberration assays in human peripheral blood lymphocytes or Chinese hamster ovary cells, and an in vivo mouse bone marrow micronucleus assay.

Impairment of Fertility

Efavirenz did not impair mating or fertility of male or female rats, and did not affect sperm of treated male rats. The reproductive performance of offspring born to female rats given efavirenz was not affected. The AUCs at the NOAEL values in male (200 mg/kg) and female (100 mg/kg) rats were approximately ≤0.15 times that in humans at the recommended clinical dose.

Animal Toxicology

Nonsustained convulsions were observed in 6 of 20 monkeys receiving efavirenz at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the recommended dose [see Warnings and Precautions (5.10)].

Adults

Study 006, a randomized, open-label trial, compared Sustiva (600 mg once daily) + zidovudine (ZDV, 300 mg q12h) + lamivudine (LAM, 150 mg q12h) or Sustiva (600 mg once daily) + indinavir (IDV, 1000 mg q8h) with indinavir (800 mg q8h) + zidovudine (300 mg q12h) + lamivudine (150 mg q12h). Twelve hundred sixty-six patients (mean age 36.5 years [range 18-81], 60% Caucasian, 83% male) were enrolled. All patients were efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry. The median baseline CD4+ cell count was 320 cells/mm3 and the median baseline HIV-1 RNA level was 4.8 log10 copies/mL. Treatment outcomes with standard assay (assay limit 400 copies/mL) through 48 and 168 weeks are shown in Table 9. Plasma HIV RNA levels were quantified with standard (assay limit 400 copies/mL) and ultrasensitive (assay limit 50 copies/mL) versions of the AMPLICOR HIV-1 MONITOR assay. During the study, version 1.5 of the assay was introduced in Europe to enhance detection of non-clade B virus.

Table 9: Outcomes of Randomized Treatment Through 48 and 168 Weeks, Study 006

	Sustiva + ZDV + LAM (n=422)		Sustiva + IDV (n=429)		IDV + ZDV + LAM (n=415)
Outcome	Week 48	Week 168	Week 48	Week 168	Week 48	Week 168
a  Patients achieved and maintained confirmed HIV-1 RNA <400 copies/mL through Week 48 or Week 168. b  Includes patients who rebounded, patients who were on study at Week 48 and failed to achieve confirmed HIV-1 RNA <400 copies/mL at time of discontinuation, and patients who discontinued due to lack of efficacy. c  Includes consent withdrawn, lost to follow-up, noncompliance, never treated, missing data, protocol violation, death, and other reasons. Patients with HIV-1 RNA levels <400 copies/mL who chose not to continue in the voluntary extension phases of the study were censored at date of last dose of study medication.
Respondera	69%	48%	57%	40%	50%	29%
Virologic failureb	6%	12%	15%	20%	13%	19%
Discontinued for adverse events	7%	8%	6%	8%	16%	20%
Discontinued for other reasonsc	17%	31%	22%	32%	21%	32%
CD4+ cell count (cells/mm3)
Observed subjects (n)	(279)	(205)	(256)	(158)	(228)	(129)
Mean change from baseline	190	329	191	319	180	329

For patients treated with Sustiva + zidovudine + lamivudine, Sustiva + indinavir, or indinavir + zidovudine + lamivudine, the percentage of responders with HIV-1 RNA <50 copies/mL was 65%, 50%, and 45%, respectively, through 48 weeks, and 43%, 31%, and 23%, respectively, through 168 weeks. A Kaplan-Meier analysis of time to loss of virologic response (HIV RNA <400 copies/mL) suggests that both the trends of virologic response and differences in response continue through 4 years.

ACTG 364 is a randomized, double-blind, placebo-controlled, 48-week study in NRTI-experienced patients who had completed two prior ACTG studies. One-hundred ninety-six patients (mean age 41 years [range 18-76], 74% Caucasian, 88% male) received NRTIs in combination with Sustiva (600 mg once daily), or nelfinavir (NFV, 750 mg three times daily), or Sustiva (600 mg once daily) + nelfinavir in a randomized, double-blinded manner. The mean baseline CD4+ cell count was 389 cells/mm3 and mean baseline HIV-1 RNA level was 8130 copies/mL. Upon entry into the study, all patients were assigned a new open-label NRTI regimen, which was dependent on their previous NRTI treatment experience. There was no significant difference in the mean CD4+ cell count among treatment groups; the overall mean increase was approximately 100 cells at 48 weeks among patients who continued on study regimens. Treatment outcomes are shown in Table 10. Plasma HIV RNA levels were quantified with the AMPLICOR HIV-1 MONITOR assay using a lower limit of quantification of 500 copies/mL.

Table 10: Outcomes of Randomized Treatment Through 48 Weeks, Study ACTG 364*

Outcome	Sustiva + NFV + NRTIs (n=65)	Sustiva + NRTIs (n=65)	NFV + NRTIs (n=66)
*  For some patients, Week 56 data were used to confirm the status at Week 48. a  Subjects achieved virologic response (two consecutive viral loads <500 copies/mL) and maintained it through Week 48. b  Includes viral rebound and failure to achieve confirmed <500 copies/mL by Week 48. c  See Adverse Reactions (6.1) for a safety profile of these regimens. d  Includes loss to follow-up, consent withdrawn, noncompliance.
HIV-1 RNA <500 copies/mLa	71%	63%	41%
HIV-1 RNA ≥500 copies/mLb	17%	34%	54%
CDC Category C Event	2%	0%	0%
Discontinuations for adverse eventsc	3%	3%	5%
Discontinuations for other reasonsd	8%	0%	0%

A Kaplan-Meier analysis of time to treatment failure through 72 weeks demonstrates a longer duration of virologic suppression (HIV RNA <500 copies/mL) in the Sustiva-containing treatment arms.

Pediatric Patients

Study AI266922 is an open-label study to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of Sustiva in combination with didanosine and emtricitabine in antiretroviral-naive and -experienced pediatric patients. Thirty-seven patients 3 months to 6 years of age (median 0.7 years) were treated with Sustiva. At baseline, median plasma HIV-1 RNA was 5.88 log10 copies/mL, median CD4+ cell count was 1144 cells/mm3, and median CD4+ percentage was 25%. The median time on study therapy was 60 weeks; 27% of patients discontinued before Week 48. Using an ITT analysis, the overall proportions of patients with HIV RNA <400 copies/mL and <50 copies/mL at Week 48 were 57% (21/37) and 46% (17/37), respectively. The median increase from baseline in CD4+ count at 48 weeks was 196 cells/mm3 and the median increase in CD4+ percentage was 6%.

Study PACTG 1021 was an open-label study to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of Sustiva in combination with didanosine and emtricitabine in pediatric patients who were antiretroviral therapy naive. Forty-three patients 3 months to 21 years of age (median 9.6 years) were dosed with Sustiva. At baseline, median plasma HIV-1 RNA was 4.8 log10 copies/mL, median CD4+ cell count was 367 cells/mm3, and median CD4+ percentage was 18%. The median time on study therapy was 181 weeks; 16% of patients discontinued before Week 48. Using an ITT analysis, the overall proportions of patients with HIV RNA <400 copies/mL and <50 copies/mL at Week 48 were 77% (33/43) and 70% (30/43), respectively. The median increase from baseline in CD4+ count at 48 weeks of therapy was 238 cells/mm3 and the median increase in CD4+ percentage was 13%.

Study PACTG 382 was an open-label study to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of Sustiva in combination with nelfinavir and an NRTI in antiretroviral-naive and NRTI-experienced pediatric patients. One hundred two patients 3 months to 16 years of age (median 5.7 years) were treated with Sustiva. Eighty-seven percent of patients had received prior antiretroviral therapy. At baseline, median plasma HIV-1 RNA was 4.57 log10 copies/mL, median CD4+ cell count was 755 cells/mm3, and median CD4+ percentage was 30%. The median time on study therapy was 118 weeks; 25% of patients discontinued before Week 48. Using an ITT analysis, the overall proportion of patients with HIV RNA <400 copies/mL and <50 copies/mL at Week 48 were 57% (58/102) and 43% (44/102), respectively. The median increase from baseline in CD4+ count at 48 weeks of therapy was 128 cells/mm3 and the median increase in CD4+ percentage was 5%.

Sustiva® (sus-TEE-vah)
(efavirenz)
capsules

Preparing a dose of Sustiva using the capsule sprinkle method

Read this Instructions for Use before you prepare your first dose of Sustiva mixed with food or infant formula using the capsule sprinkle method, each time you get a refill, and as needed. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment. Ask your doctor or pharmacist if you have any questions about how to mix or give a dose of Sustiva using the capsule sprinkle method.

Important Information:

• For more information about Sustiva capsules, see the Patient Information leaflet.
• The capsule sprinkle method for mixing the contents of Sustiva capsules with soft food or infant formula may be used for adults or children who cannot swallow capsules or tablets.
• You should take Sustiva on an empty stomach at bedtime.
• You should not eat for 2 hours after taking Sustiva mixed with food.
• Babies who are old enough to swallow food should be given Sustiva using the capsule sprinkle method mixed with food instead of with infant formula.
• Talk with your doctor to help decide the best schedule for giving your baby Sustiva mixed with infant formula using the capsule sprinkle method.

Preparing a dose of Sustiva mixed with food using the capsule sprinkle method.

Before you prepare a dose of Sustiva mixed with food using the capsule sprinkle method, gather the following supplies:

• paper towels
• teaspoon for measuring
• small spoon for stirring and feeding
• small clean container (such as a small cup or bowl)
• soft food such as applesauce, grape jelly, or yogurt

Step 1. Choose a clean, flat work surface. Place a clean paper towel on the work surface. Then place the other supplies on the paper towel.
Step 2. Wash and dry your hands well.
Step 3. Place 1 to 2 teaspoons of soft food such as applesauce, grape jelly, or yogurt in the small container (see Figure A). The color and thickness of the food may change when mixed with the medicine.	Figure A
Step 4. There are 2 parts of the Sustiva capsule. Look at the Sustiva capsule to see which part of the capsule overlaps the other part (see Figure B).	Figure B
Step 5. Hold the Sustiva capsule in a sideways (horizontal) position directly over the container of food. Hold each end of the Sustiva capsule between your thumbs and index (pointer) fingers (see Figure C).	Figure C
Step 6. Use your thumb and index finger to pinch near the end of the overlapping part of the Sustiva capsule (see Figure D).	Figure D
Then, carefully twist both ends of the Sustiva capsule in opposite directions to open it (see Figure E). Be careful not to spill the capsule contents or spread it in the air.	Figure E
Step 7. Sprinkle the contents of the Sustiva capsule onto the food (see Figure F). •Check the capsule shells to make sure they are empty.•Throw away the empty capsule shells.	Figure F
If the total prescribed dose is more than 1 capsule, follow Steps 4 through 7 for each capsule. Do not add more food.
Steps 8 through 11 should be completed within 30 minutes of mixing the medicine (see Figure G).	Figure G
Step 8. Use the small spoon to gently mix the capsule contents and food together (see Figure H). Sprinkles will not dissolve. Mixture will look grainy but should not be lumpy.	Figure H
Step 9. Use the small spoon to give or take the food and capsule contents mixture. Make sure that all of the mixture is swallowed.
Step 10. Add about 2 teaspoons more of the food to the empty container and gently stir with the small spoon to mix with any capsule contents that may still be in the container.
Step 11. Use the small spoon to give or take the food and capsule contents mixture. Make sure all of the mixture is swallowed.
Step 12. Wash the container and spoons. Throw away the paper towel and clean the work surface. Wash your hands.
Preparing a dose of Sustiva mixed with infant formula using the capsule sprinkle method
To make sure that your baby gets all of the medicine, do not give Sustiva capsule contents to your baby in a bottle.
Before you prepare a dose of Sustiva mixed with infant formula using the capsule sprinkle method, gather the following supplies:
paper towels teaspoon for stirring and measuring small clean container (such as a small cup or bowl) (see Figure I). 10 mL oral dosing syringe (ask your pharmacist for this) (see Figure I). infant formula at room temperature.	Figure I
Step 1. Prepare the infant formula according to the directions on the infant formula package. You will use about 1 ounce of the formula to give the medicine. Any remaining formula should not be given to the child for 2 hours.
Step 2. Choose a clean, flat work surface. Place a clean paper towel on the work surface. Place the supplies you will need on the paper towel.
Step 3. Wash and dry your hands well.
Step 4. Pour 2 teaspoons of room temperature infant formula into the container (see Figure J).	Figure J
Step 5. There are 2 parts of the Sustiva capsule. Look at the Sustiva capsule to see which part of the capsule overlaps the other part (see Figure K).	Figure K
Step 6. Hold the Sustiva capsule in a sideways (horizontal) position directly over the container with the infant formula. Hold each end of the Sustiva capsule between your thumbs and index (pointer) fingers (see Figure L).	Figure L
Step 7. Use your thumb and index finger to pinch near the end of the overlapping part of the Sustiva capsule (see Figure M).	Figure M
Then, carefully twist both ends of the Sustiva capsule in opposite directions to open it (see Figure N). Be careful not to spill the capsule contents or spread it in the air.	Figure N
Step 8. Sprinkle the contents of the Sustiva capsule onto the infant formula (see Figure O). •Check the capsule shells to make sure they are empty.•Throw away the empty capsule shells.	Figure O
If the total prescribed dose is more than 1 capsule, follow Steps 5 through 8 for each capsule. Do not add more infant formula.
Steps 9 through 12 should be completed within 30 minutes of mixing the medicine (see Figure P).	Figure P
Step 9. Hold the container with one hand. With your other hand, use the teaspoon to gently mix the capsule contents and the infant formula (see Figure Q). Sprinkles will not dissolve. Mixture will look grainy but should not be lumpy.	Figure Q
Step 10. To draw up all of the mixture into the oral dosing syringe: •Check that the plunger is completely pushed into barrel of the syringe (see Figure R).	Figure R
•Place the tip of the syringe into the mixture in the container (see Figure S).	Figure S
•Slowly pull back on the plunger and draw up all of the mixture (see Figure T).	Figure T
Step 11. Place the tip of the syringe in your baby’s mouth along the inner cheek (see Figure U). Slowly push on the plunger to give your baby all of the mixture.	Figure U
Step 12. To make sure all of the medicine is given to your baby: •Repeat Step 4 above.•Stir with a teaspoon.•Then, repeat Steps 10 and 11 above (see Figure V).	Figure V
Step 13. Remove the plunger from the oral dosing syringe. Wash the container, teaspoon, and oral dosing syringe. Allow the plunger and the syringe barrel to dry before putting them back together.
Step 14. Throw away the paper towel and clean the work surface. Wash your hands.

How should I store Sustiva capsules?

•Store Sustiva capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep Sustiva capsules and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Distributed by:

Bristol-Myers Squibb Company
Princeton, NJ 08543 USA

Revised: January 2017

Do not take Sustiva together with Atripla (combination efavirenz, emtricitabine, and tenofovir), unless your doctor tells you to.

Do not take Sustiva with cisapride (Propulsid), pimozide (Orap), midazolam (Versed), triazolam (Halcion), or ergot medicines such as dihydroergotamine (D.H.E. 45), ergonovine (Ergotrate), ergotamine (Ergomar, Cafergot, Wigraine), or methylergonovine (Methergine). These drugs can cause life-threatening side effects if you use them while you are taking efavirenz.

Sustiva may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.

Do not use Sustiva without telling your doctor if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking this medicine, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment.

Taking Sustiva will not prevent you from passing HIV to other people. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Common side effects of Sustiva include: diarrhea, nausea, and skin rash. Other side effects include: dizziness, lack of concentration, fatigue, headache, vomiting, and anorexia. See below for a comprehensive list of adverse effects.