Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Nevirapine is structurally a member of the dipyridodiazepinone chemical class of compounds. The chemical name of nevirapine is 11-cyclopropyl-5, 11-dihydro-4-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4] diazepin-6-one. Nevirapine is a white to off-white crystalline powder with the molecular weight of 266.30 and the molecular formula C 15 H 14 N 4 O. Nevirapine has the following structural formula: Nevirapine extended-release tablets, USP are for oral administration. Each tablet contains 400 mg of nevirapine USP and the inactive ingredients lactose monohydrate, hypromellose, ferric oxide, povidone and magnesium stearate. str

Nevirapine extended-release tablets are indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults and pediatric patients 6 years of age or older with a body surface area (BSA) of 1.17 m 2 or greater . Limitations of Use: Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine extended-release tablets are not recommended to be initiated, unless the benefit outweighs the risk, in: • adult females with CD4 + cell counts greater than 250 cells/mm 3 or • adult males with CD4 + cell counts greater than 400 cells/mm 3 . • Nevirapine extended-release tablets are an NNRTI indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults and pediatric patients 6 years of age or older with a BSA of 1.17 m 2 or greater. Limitations of Use: Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine extended-release tablets are not recommended to be initiated, unless the benefit outweighs the risk, in: • adult females with CD4 + cell counts greater than 250 cells/mm 3 • adult males with CD4 + cell counts greater than 400 cells/mm 3

DOSAGE FORMS & STRENGTHS Nevirapine extended-release tablets, USP 400 mg are yellow coloured, oval shaped, biconvex tablets, debossed with 'C11' on one side and plain on the other side. • 400 mg extended-release tablets

• The 14-day lead-in period with immediate-release nevirapine tablets (200 mg once daily) must be strictly followed; it has been demonstrated to reduce the frequency of rash. • Must be swallowed whole and must not be chewed, crushed, or divided. • Adult patients must initiate therapy with one 200 mg immediate-release nevirapine tablet once daily for the first 14 days, followed by one 400 mg tablet of nevirapine extended-release tablets once daily. • Adult patients already on a regimen of immediate-release nevirapine tablets twice daily can be switched to nevirapine extended-release tablets 400 mg once daily without the 14-day lead-in period of immediate-release nevirapine tablets. • Pediatric patients (ages 6 to less than 18 years with a BSA of 1.17 m 2 or greater) must initiate therapy with immediate-release nevirapine tablets (as 150 mg/m2 of Nevirapine Oral Suspension or as nevirapine tablet) at a dose not to exceed 200 mg per day administered once daily for the first 14 days, followed by nevirapine extended-release tablets 400 mg once daily. • Pediatric patients with a BSA of 1.17 m 2 or greater already on a regimen of twice daily nevirapine tablets Oral Suspension or immediate-release nevirapine can be switched to nevirapine extended-release tablets 400 mg once daily without the 14-day lead-in period of nevirapine Oral Suspension or immediate-release nevirapine tablets. • If any patient experiences rash during the 14-day lead-in period with immediate-release nevirapine tablets do not initiate nevirapine extended-release tablets until the rash has resolved. Do not continue the immediate-release nevirapine tablets lead-in dosing regimen beyond 28 days. • If dosing is interrupted for greater than 7 days, restart 14-day lead-in dosing

General Dosing Considerations Nevirapine extended-release tablets must be swallowed whole and must not be chewed, crushed, or divided. Pediatric patients should be assessed for their ability to swallow the extended-release tablets before prescribing nevirapine extended-release tablets. Nevirapine extended-release tablets can be taken with or without food

Recommended Dosage in Adult Patients Patients not currently taking immediate-release nevirapine Patients must initiate therapy with one 200-mg tablet of immediate-release nevirapine tablets daily for the first 14 days in combination with other antiretroviral agents. The 14-day lead-in period with nevirapine tablets 200 mg daily dosing must be strictly followed (the lead-in period has been observed to decrease the incidence of rash), followed by one 400-mg tablet of nevirapine extended-release tablets once daily . If rash persists beyond the 14-day lead-in period with immediate-release nevirapine tablets, do not begin dosing with nevirapine extended-release tablets. The lead-in dosing with 200 mg once daily immediate-release nevirapine tablets should not be continued beyond 28 days, at which point an alternative regimen should be sought. Switching patients from immediate-release nevirapine tablets to nevirapine extended-release tablets Patients already on a regimen of immediate-release nevirapine tablets twice daily in combination with other antiretroviral agents can be switched to nevirapine extended-release tablets 400 mg once daily without the 14-day lead-in period. Patients already on a regimen of immediate-release nevirapine tablets twice daily who switch to nevirapine extended-release tablets therapy should continue with their ongoing clinical and laboratory monitoring

Recommended Dosage in Pediatric Patients Nevirapine extended-release tablet in pediatric patients is dosed based on body surface area (BSA) calculated using the Mosteller formula. All pediatric patients must initiate therapy with immediate-release nevirapine tablets (as 150 mg/m 2 of Nevirapine Oral Suspension or as nevirapine tablets), at a dose not to exceed 200 mg per day, administered once daily for the first 14 days. This lead-in period should be used because it has been demonstrated to reduce the frequency of rash. This lead-in period is not required if the patient is already on a regimen of twice daily immediate-release formulation in combination with other antiretroviral agents. The recommended oral dosage of nevirapine extended-release tablets for pediatric patients with a BSA of 1.17 m 2 or greater is 400 mg following the lead-in period with immediate-release nevirapine tablets. The total daily dose should not exceed 400 mg for any patient. formula 2.4 Monitoring of Patients Intensive clinical and laboratory monitoring, including liver enzyme tests, is essential at baseline and during the first 18 weeks of treatment with nevirapine. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, would include monitoring of liver enzyme tests prior to beginning the 14-day lead-in period with immediate-release nevirapine tablets, prior to initiation of nevirapine extended-release tablets, and at two weeks after initiation of nevirapine extended-release tablets therapy. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine extended-release tablets treatment . In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients already on a regimen of immediate-release nevirapine tablets twice daily who switch to nevirapine extended-release tablets once daily should continue with their ongoing clinical and laboratory monitoring

Dosage Adjustment Patients with Rash Discontinue nevirapine if a patient experiences severe rash or any rash accompanied by constitutional findings . Do not initiate therapy with nevirapine extended-release tablets if a patient experiences mild to moderate rash without constitutional symptoms during the 14-day lead-in period of immediate-release nevirapine tablets until the rash has resolved . The total duration of the once daily lead-in dosing period should not exceed 28 days, at which point an alternative regimen should be sought. Patients with Hepatic Events If a clinical (symptomatic) hepatic event occurs, permanently discontinue nevirapine. Do not restart nevirapine after recovery . Patients with Dose Interruption For patients who interrupt nevirapine extended-release tablets dosing for more than 7 days, restart the recommended lead-in dosing with immediate-release nevirapine tablets, using one 200 mg tablet daily for the first 14 days. Patients with Renal Impairment Patients with CrCl greater than or equal to 20 mL per min and not requiring dialysis do not require an adjustment in dosing. The pharmacokinetics of nevirapine have not been evaluated in patients with CrCl less than 20 mL per min. An additional 200 mg dose of immediate-release nevirapine tablets following each dialysis treatment is indicated in patients requiring dialysis. Nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known . Nevirapine extended-release tablets have not been studied in patients with renal dysfunction.

• Monitor patients for immune reconstitution syndrome and fat redistribution. 5.1 Hepatotoxicity and Hepatic Impairment Severe, life-threatening, and in some cases fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis and hepatic failure, have been reported in patients treated with nevirapine. The risk of symptomatic hepatic events regardless of severity is greatest in the first 6 weeks of therapy. The risk continued to be greater in the nevirapine groups in controlled clinical trials through 18 weeks of treatment. However, hepatic events may occur at any time during treatment. In some cases, patients presented with non-specific, prodromal signs or symptoms of fatigue, malaise, anorexia, nausea, jaundice, liver tenderness or hepatomegaly, with or without initially abnormal serum transaminase levels. Rash was observed in approximately half of the patients with symptomatic hepatic adverse events. Fever and flu-like symptoms accompanied some of these hepatic events. Some events, particularly those with rash and other symptoms, have progressed to hepatic failure with transaminase elevation, with or without hyperbilirubinemia, hepatic encephalopathy, prolonged partial thromboplastin time, or eosinophilia. Rhabdomyolysis has been observed in some patients experiencing skin and/or liver reactions associated with nevirapine use. Hepatitis/hepatic failure may be associated with signs of hypersensitivity which can include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction. Patients with signs or symptoms of hepatitis must be advised to discontinue nevirapine and immediately seek medical evaluation, which should include liver enzyme tests. The first 18 weeks of therapy with nevirapine extended-release tablets are a critical period during which intensive clinical and laboratory monitoring of patients is required to detect potentially life-threatening hepatic events. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, include monitoring of liver enzyme tests at baseline, prior to dose escalation and at two weeks post-dose escalation. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine extended-release tablets treatment. Transaminases should be checked immediately if a patient experiences signs or symptoms suggestive of hepatitis and/or hypersensitivity reaction. Transaminases should also be checked immediately for all patients who develop a rash in the first 18 weeks of treatment. Physicians and patients should be vigilant for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness, or hepatomegaly. The diagnosis of hepatotoxicity should be considered in this setting, even if transaminases are initially normal or alternative diagnoses are possible . If clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, permanently discontinue nevirapine. Do not restart nevirapine after recovery. In some cases, hepatic injury progresses despite discontinuation of treatment. The patients at greatest risk of hepatic events, including potentially fatal events, are women with high CD4 + cell counts. In a retrospective analysis of pooled clinical trials with immediate-release nevirapine tablets, during the first 6 weeks of treatment women had a 3-fold higher risk than men for symptomatic, often rash-associated, hepatic events (6% versus 2%). Patients with higher CD4 + cell counts at initiation of nevirapine therapy are at higher risk for symptomatic hepatic events. Women with CD4 + cell counts greater than 250 cells/mm 3 had a 12-fold higher risk of symptomatic hepatic adverse events compared to women with CD4 + cell counts less than 250 cells/mm 3 (11% versus 1%). An increased risk was observed in men with CD4 + cell counts greater than 400 cells/mm 3 (6% versus 1% for men with CD4 + cell counts less than 400 cells/mm 3 ). However, all patients, regardless of sex, CD4 + cell count, or antiretroviral treatment history, should be monitored for hepatotoxicity since symptomatic hepatic adverse events have been reported at all CD4 + cell counts. Co-infection with hepatitis B or C or transaminase elevations at the start of therapy with nevirapine are associated with a greater risk of later symptomatic events (6 weeks or more after starting nevirapine) and asymptomatic increases in AST or ALT. In addition, serious hepatotoxicity (including liver failure requiring transplantation in one instance) has been reported in HIV-1 uninfected individuals receiving multiple doses of immediate-release nevirapine tablets in the setting of post-exposure prophylaxis (PEP), an unapproved use. Use of nevirapine extended-release tablets for occupational and non-occupational PEP is contraindicated . Increased nevirapine trough concentrations have been observed in some patients with hepatic fibrosis or cirrhosis. Therefore, carefully monitor patients with either hepatic fibrosis or cirrhosis for evidence of drug-induced toxicity. Do not administer nevirapine to patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment . Nevirapine extended-release tablets have not been evaluated in subjects with hepatic impairment

Skin Reactions Severe and life-threatening skin reactions, including fatal cases, have been reported in patients taking nevirapine. These have occurred most frequently during the first 6 weeks of therapy. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction including hepatic failure. Rhabdomyolysis has been observed in some patients experiencing skin and/or liver reactions associated with nevirapine use. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, and/or hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and renal dysfunction) must permanently discontinue nevirapine and seek medical evaluation immediately. Do not restart nevirapine following severe skin rash, skin rash combined with increased transaminases or other symptoms, or hypersensitivity reaction. The first 18 weeks of therapy with nevirapine extended-release tablets are a critical period during which intensive clinical and laboratory monitoring of patients is required to detect potentially life-threatening skin reactions. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, include monitoring of liver enzyme tests at baseline, prior to dose escalation and at two weeks post-dose escalation. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine extended-release tablets treatment. In addition, the 14-day lead-in period with immediate-release nevirapine tablets 200 mg daily dosing has been demonstrated to reduce the frequency of rash . If patients present with a suspected nevirapine-associated rash, measure transaminases immediately. Permanently discontinue nevirapine in patients with rash-associated transaminase elevations . Patients must initiate therapy with immediate-release nevirapine tablets daily for the first 14 days. This lead-in period has been shown to reduce the frequency of rash. Discontinue nevirapine if a patient experiences severe rash or any rash accompanied by constitutional findings. Do not initiate nevirapine extended-release tablets if patient is experiencing a mild to moderate rash without constitutional symptoms during the 14-day immediate-release nevirapine tablets lead-in period of 200 mg/day (150 mg/m 2 /day in pediatric patients) until the rash has resolved. The total duration of the immediate-release nevirapine tablets lead-in dosing period must not exceed 28 days, at which point an alternative regimen should be sought . Patients must be monitored closely if isolated rash of any severity occurs. Delay in stopping nevirapine treatment after the onset of rash may result in a more serious reaction. Women appear to be at higher risk than men of developing rash with nevirapine. In a clinical trial of immediate-release nevirapine tablets, concomitant prednisone use (40 mg per day for the first 14 days of nevirapine administration) was associated with an increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy. Therefore, use of prednisone to prevent nevirapine-associated rash is not recommended

Resistance Nevirapine extended-release tablets must not be used as a single agent to treat HIV-1 or added on as a sole agent to a failing regimen. Resistant virus emerges rapidly when nevirapine is administered as monotherapy. The choice of new antiretroviral agents to be used in combination with nevirapine should take into consideration the potential for cross resistance. When discontinuing an antiretroviral regimen containing nevirapine extended-release tablets, the long half-life of nevirapine should be considered; if antiretrovirals with shorter half-lives than nevirapine are stopped concurrently, low plasma concentrations of nevirapine alone may persist for a week or longer and virus resistance may subsequently develop

Drug Interactions See Table 3 for listings of established and potential drug interactions . Concomitant use of St. John's wort (Hypericum perforatum) or St. John's wort-containing products and nevirapine is not recommended. Co-administration of St. John’s wort with non-nucleoside reverse transcriptase inhibitors (NNRTIs), including nevirapine, is expected to substantially decrease NNRTI concentrations and may result in sub-optimal levels of nevirapine and lead to loss of virologic response and possible resistance to nevirapine or to the class of NNRTIs. Co-administration of nevirapine and efavirenz is not recommended as this combination has been associated with an increase in adverse reactions and no improvement in efficacy

Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including nevirapine. 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, 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.

Nevirapine is principally metabolized by the liver via the cytochrome P450 isoenzymes, 3A and 2B6. Nevirapine is known to be an inducer of these enzymes. As a result, drugs that are metabolized by these enzyme systems may have lower than expected plasma levels when co-administered with nevirapine. The results of drug interactions studies with immediate-release nevirapine tablets are expected to also apply to nevirapine extended-release tablets. The specific pharmacokinetic changes that occur with co-administration of nevirapine and other drugs are listed in Clinical Pharmacology , Table 4. Clinical comments about possible dosage modifications based on established drug interactions are listed in Table 3. The data in Tables 3 and 4 are based on the results of drug interaction studies conducted in HIV-1 seropositive subjects unless otherwise indicated. In addition to established drug interactions, there may be potential pharmacokinetic interactions between nevirapine and other drug classes that are metabolized by the cytochrome P450 system. These potential drug interactions are also listed in Table 3. Although specific drug interaction studies in HIV-1 seropositive subjects have not been conducted for some classes of drugs listed in Table 3, additional clinical monitoring may be warranted when co-administering these drugs. The in vitro interaction between nevirapine and the antithrombotic agent warfarin is complex. As a result, when giving these drugs concomitantly, plasma warfarin levels may change with the potential for increases in coagulation time. When warfarin is co-administered with nevirapine, anticoagulation levels should be monitored frequently. Table 3 Established and Potential Drug Interactions: Use with Caution, Alteration in Dose or Regimen May Be Needed Due to Drug Interaction Established Drug Interactions: See Clinical Pharmacology, Table 4 for Magnitude of Interaction. Drug Name Effect on Concentration of Nevirapine or Concomitant Drug Clinical Comment HIV Antiviral Agents: Protease Inhibitors (PIs) Atazanavir/Ritonavir* ↓ Atazanavir ↑ Nevirapine Do not co-administer nevirapine with atazanavir because nevirapine substantially decreases atazanavir exposure and there is a potential risk for nevirapine-associated toxicity due to increased nevirapine exposures. Fosamprenavir* ↓Amprenavir ↑Nevirapine Co-administration of nevirapine and fosamprenavir without ritonavir is not recommended. Fosamprenavir/Ritonavir* ↓Amprenavir ↑Nevirapine No dosing adjustments are required when nevirapine is co-administered with 700/100 mg of fosamprenavir/ritonavir twice daily. The combination of nevirapine administered with fosamprenavir/ritonavir once daily has not been studied. Indinavir* ↓ Indinavir The appropriate doses of this combination of indinavir and nevirapine with respect to efficacy and safety have not been established. Lopinavir/Ritonavir* ↓Lopinavir Dosing in adult patients: A dose adjustment of lopinavir/ritonavir to 500/125 mg tablets twice daily or 533/133 mg (6.5 mL) oral solution twice daily is recommended when used in combination with nevirapine. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine. Dosing in pediatric patients: Please refer to the Kaletra® prescribing information for dosing recommendations based on body surface area and body weight. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine. Nelfinavir* ↓Nelfinavir M8 Metabolite ↓Nelfinavir C min The appropriate doses of the combination of nevirapine and nelfinavir with respect to safety and efficacy have not been established. Saquinavir/Ritonavir The interaction between nevirapine and saquinavir/ritonavir has not been evaluated. The appropriate doses of the combination of nevirapine and saquinavir/ritonavir with respect to safety and efficacy have not been established. HIV Antiviral Agents: Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Efavirenz* Etravirine Rilpivirine ↓ Efavirenz The appropriate doses of these combinations with respect to safety and efficacy have not been established. Plasma concentrations may be altered. Nevirapine should not be coadministered with another NNRTI as this combination has not been shown to be beneficial. Other Agents Analgesics: Methadone* ↓ Methadone Methadone levels were decreased; increased dosages may be required to prevent symptoms of opiate withdrawal. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly. Antiarrhythmics: Amiodarone, disopyramide, lidocaine Plasma concentrations may be decreased. Appropriate doses for this combination have not been established. Antibiotics: Clarithromycin* ↓ Clarithromycin ↑ 14-OH clarithromycin Clarithromycin exposure was significantly decreased by nevirapine; however, 14-OH metabolite concentrations were increased. Because clarithromycin active metabolite has reduced activity against Mycobacterium aviumintracellulare complex , overall activity against this pathogen may be altered. Alternatives to clarithromycin, such as azithromycin, should be considered. Rifabutin* ↑Rifabutin Rifabutin and its metabolite concentrations were moderately increased. Due to high intersubject variability, however, some patients may experience large increases in rifabutin exposure and may be at higher risk for rifabutin toxicity. Therefore, caution should be used in concomitant administration. Rifampin* ↓ Nevirapine Nevirapine and rifampin should not be administered concomitantly because decreases in nevirapine plasma concentrations may reduce the efficacy of the drug. Physicians needing to treat patients co-infected with tuberculosis and using a nevirapine-containing regimen may use rifabutin instead. Anticonvulsants: Carbamazepine, clonazepam, ethosuximide Plasma concentrations of nevirapine and the anticonvulsant may be decreased. Use with caution and monitor virologic response and levels of anticonvulsants. Antifungals: Fluconazole* ↑Nevirapine Because of the risk of increased exposure to nevirapine, caution should be used in concomitant administration, and patients should be monitored closely for nevirapine-associated adverse events. Ketoconazole* ↓ Ketoconazole Nevirapine and ketoconazole should not be administered concomitantly because decreases in ketoconazole plasma concentrations may reduce the efficacy of the drug. Itraconazole ↓ Itraconazole Nevirapine and itraconazole should not be administered concomitantly due to potential decreases in itraconazole plasma concentrations that may reduce efficacy of the drug. Antithrombotics: Warfarin Plasma concentrations may be increased. Potential effect on anticoagulation. Monitoring of anticoagulation levels is recommended. Calcium Channel Blockers: Diltiazem, nifedipine, verapamil Plasma concentrations may be decreased. Appropriate doses for these combinations have not been established. Cancer Chemotherapy: Cyclophosphamide Plasma concentrations may be decreased. Appropriate doses for this combination have not been established. Ergot Alkaloids: Ergotamine Plasma concentrations may be decreased. Appropriate doses for this combination have not been established. Immunosuppressants: Cyclosporine, tacrolimus, sirolimus Plasma concentrations may be decreased. Appropriate doses for these combinations have not been established. Opiate Agonists: Fentanyl Plasma concentrations may be decreased. Appropriate doses for this combination have not been established. Oral Contraceptives: Ethinyl Estradiol and Norethindrone* ↓ Ethinyl Estradiol ↓ Norethindrone Despite lower ethinyl estradiol and norethindrone exposures when coadministered with nevirapine, literature reports suggest that nevirapine has no effect on pregnancy rates among HIV-infected women on combined oral contraceptives. When coadministered with nevirapine extended-release tablets, no dose adjustment of ethinyl estradiol or norethindrone is needed when used in combination for contraception. When oral contraceptives are used for hormonal regulation during nevirapine extended-release tablets therapy, the therapeutic effect of the hormonal therapy should be monitored. * The interaction between immediate-release nevirapine tablets and the drug was evaluated in a clinical study. The results of drug interaction studies with immediate-release nevirapine tablets are expected to also apply to nevirapine extended-release tablets. Co-administration of nevirapine extended-release tablets can alter the concentrations of other drugs, and other drugs may alter the concentration of nevirapine. The potential for drug interactions must be considered prior to and during therapy. ( 5.4 , 7 , 12.3 )