Tenolam E

Tenolam E (brand names Tenolam E® and Tenolam E®) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1. For HIV infection that has not previously been treated, Tenolam E and lamivudine in combination with zidovudine or tenofovir is the preferred NNRTI-based regimen. Tenolam E is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to prevent HIV transmission for those exposed to materials associated with a high risk for HIV transmission.

Tenolam E® (Tenolam E) in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg.

Tenolam E is used in combination with other medicines for the treatment of the infection caused by the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Tenolam E is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It works by lowering the amount of HIV in the blood.

Tenolam E will not cure or prevent HIV infection or AIDS, however, it helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems that usually result from AIDS or HIV disease. Tenolam E will not keep you from spreading HIV to other people. People who receive Tenolam E may continue to have some of the problems usually related to AIDS or HIV disease.

Tenolam E is available only with your doctor's prescription.

Adults

The recommended dosage of Tenolam E (Tenolam E) is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs). It is recommended that Tenolam E be taken on an empty stomach, preferably at bedtime. The increased Tenolam E concentrations observed following administration of Tenolam E with food may lead to an increase in frequency of adverse reactions. Dosing at bedtime may improve the tolerability of nervous system symptoms. Tenolam E capsules or tablets should be swallowed intact with liquid. For patients who cannot swallow capsules or tablets, the capsule sprinkle method of administration is recommended.

Concomitant Antiretroviral Therapy

Tenolam E must be given in combination with other antiretroviral medications.

Dosage Adjustment

If Tenolam E is coadministered with voriconazole, the voriconazole maintenance dose should be increased to 400 mg every 12 hours and the Tenolam E dose should be decreased to 300 mg once daily using the capsule formulation (one 200 mg and two 50 mg capsules or six 50 mg capsules). Tenolam E tablets must not be broken.

If Tenolam E is coadministered with rifampin to patients weighing 50 kg or more, an increase in the dose of Tenolam E to 800 mg once daily is recommended.

Pediatric Patients

It is recommended that Tenolam E be taken on an empty stomach, preferably at bedtime. Table 1 describes the recommended dose of Tenolam E for pediatric patients 3 months of age or older and weighing between 3.5 kg and 40 kg. The recommended dosage of Tenolam E for pediatric patients weighing 40 kg or greater is 600 mg once daily. For pediatric patients who cannot swallow capsules, the capsule contents can be administered with a small amount of food or infant formula using the capsule sprinkle method of administration.

Table 1: Tenolam E Dosing in Pediatric Patients

Capsule Sprinkle Method Of Administration

For pediatric patients at least 3 months old and weighing at least 3.5 kg and adults who cannot swallow capsules or tablets, the capsule contents may be administered with a small amount (1 to 2 teaspoons) of food. Use of infant formula for mixing should only be considered for those young infants who cannot reliably consume solid foods. Patients and caregivers should be instructed to open the capsule carefully to avoid spillage or dispersion of the capsule contents into the air. The capsule should be held horizontally over a small container and carefully twisted to open. For patients able to tolerate solid foods, the entire capsule contents should be gently mixed with an age-appropriate soft food, such as applesauce, grape jelly, or yogurt, in the small container. For young infants receiving the capsule sprinkle-infant formula mixture, the entire capsule contents should be gently mixed into 2 teaspoons of reconstituted room temperature infant formula in a small container by carefully stirring with a small spoon, and then drawing up the mixture into a 10 mL oral dosing syringe for administration. After administration of the Tenolam E-food or -formula mixture, an additional small amount (approximately 2 teaspoons) of food or formula must be added to the empty mixing container, stirred to disperse any remaining Tenolam E residue, and administered to the patient. The Tenolam E-food or -formula mixture should be administered within 30 minutes of mixing. No additional food should be consumed for 2 hours after administration of Tenolam E.

Further patient instructions on the capsule sprinkle method of administration are provided in the FDA-approved patient labeling.

How supplied

Dosage Forms And Strengths

Capsules

• 200 mg capsules are gold color, reverse printed with “Tenolam E” on the body and imprinted “200 mg” on the cap.
• 50 mg capsules are gold color and white, printed with “Tenolam E” on the gold color cap and reverse printed “50 mg” on the white body.

Tablets

• 600 mg tablets are yellow, capsular-shaped, film-coated tablets, with “Tenolam E” printed on both sides.

Storage And Handling

Capsules

Tenolam E® (Tenolam E) capsules are available as follows:

Capsules 200 mg are gold color, reverse printed with “Tenolam E” on the body and imprinted “200 mg” on the cap.

Bottles of 90 NDC 0056-0474-92

Capsules 50 mg are gold color and white, printed with “Tenolam E” on the gold color cap and reverse printed “50 mg” on the white body.

Bottles of 30 NDC 0056-0470-30

Tablets

Tenolam E® (Tenolam E) tablets are available as follows: Tablets 600 mg are yellow, capsular-shaped, film-coated tablets, with “Tenolam E” printed on both sides.

Bottles of 30 NDC 0056-0510-30

Storage

Tenolam E capsules and Tenolam E tablets should be stored at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).

Distributed by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA. [print code] Revised: Oct 2016

See also:
What is the most important information I should know about Tenolam E?

Do not use Tenolam E 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 Tenolam E, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment.

Tenolam E 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 take Tenolam E 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 Tenolam E.

There are many other medicines that can interact with Tenolam E, or make it less effective. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Taking this medication 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.

Use Tenolam E capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Tenolam E capsules. Talk to your pharmacist if you have questions about this information.
• Take Tenolam E capsules by mouth on an empty stomach. Taking Tenolam E capsules with food, especially with a high-fat meal, may lead to increased blood levels of Tenolam E capsules. This may increase your risk of side effects.
• Take Tenolam E capsules with a full glass of water (8 oz [240 mL]).
• Swallow Tenolam E capsules whole. Do not break, crush, or chew before swallowing. If you cannot swallow the capsule whole, you may open it and sprinkle the contents over a small amount of soft food (eg, applesauce, yogurt) or formula. Follow the detailed instructions in the patient leaflet. Swallow the mixture within 30 minutes. Do not store the mixture for future use. Check with your doctor or pharmacist if you are unsure how to mix Tenolam E capsules.
• If you take Tenolam E capsules by sprinkling it over food, do not eat any more food for 2 hours after taking a dose.
• Do NOT take more than the recommended dose, change your dose, or stop taking Tenolam E capsules without checking with your doctor.
• Take Tenolam E capsules at the same time every day, preferably at bedtime unless otherwise directed by your doctor.
• Continue to use Tenolam E capsules even if you feel well. Do not miss any doses.
• If you miss a dose of Tenolam E capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tenolam E capsules.

Tenolam E is used in combination with other medications for the treatment of human immunodeficiency virus (HIV) infection.

See also:
What other drugs will affect Tenolam E?

Tenolam E is an inducer of CYP3A4. Other compounds that are substrates of CYP3A4 may have decreased plasma concentrations when co-administered with Tenolam E.

Amprenavir: When amprenavir (1200 mg every 12 hrs) was given with Tenolam E (600 mg once daily) in HIV-infected subjects, decreases were seen in amprenavir C_max (33%), AUC (24%) and C_min (43%). While the clinical significance of decreased amprenavir concentrations has not been established, the magnitude of the observed pharmacokinetic interaction should be taken into consideration when choosing a regimen containing both Tenolam E and amprenavir.

Indinavir: When indinavir (800 mg every 8 hrs) was given with Tenolam E, the indinavir AUC and C_max were decreased by approximately 31% and 16%, respectively as a result of enzyme induction. Therefore, the dose of indinavir should be increased from 800-1000 mg every 8 hrs when Tenolam E and indinavir are co-administered. No adjustment of the dose of Tenolam E is necessary when given with indinavir.

Ritonavir: When Tenolam E 600 mg (given once daily at bedtime) and ritonavir 500 mg (given every 12 hrs) was studied in uninfected volunteers, the combination was not well tolerated and was associated with a higher frequency of adverse clinical experiences (eg, dizziness, nausea, paresthesia) and laboratory abnormalities (elevated liver enzymes). Monitoring of liver enzymes is recommended when Tenolam E is used in combination with ritonavir.

Saquinavir: When saquinavir (1200 mg given 3 times a day, soft gel formulation) was given with Tenolam E, the saquinavir AUC and C_max were decreased by 62% and 45-50%, respectively. Use of Tenolam E in combination with saquinavir as the sole protease inhibitor is not recommended.

Rifamycins: Rifampin reduced Tenolam E AUC by 26% and C_max by 20% in 12 uninfected volunteers. The dose of Tenolam E should be increased to 800 mg/day when taken with rifampin. No dose adjustment of rifampin is recommended when given with Tenolam E. In 1 study in uninfected volunteers, Tenolam E induced a reduction in rifabutin C_max and AUC by 32% and 38%, respectively and increased rifabutin clearance. Rifabutin had no significant effect on the pharmacokinetics of Tenolam E. These data suggest that the daily dose of rifabutin should be increased by 50% when administered with Tenolam E and that the rifabutin dose may be doubled for regimens in which rifabutin is given 2 or 3 times a week in combination with Tenolam E.

Clarithromycin: Co-administration of 400 mg of Tenolam E once daily with clarithromycin given as 500 mg every 12 hrs for 7 days resulted in a significant effect of Tenolam E on the pharmacokinetics of clarithromycin. The AUC and C_max of clarithromycin decreased 39% and 26%, respectively, while the AUC and C_max of the clarithromycin hydroxymetabolite were increased 34% and 49%, respectively, when used in combination with Tenolam E. The clinical significance of these changes in clarithromycin plasma levels is not known. In uninfected volunteers 46% developed rash while receiving Tenolam E and clarithromycin. No dose adjustment of Tenolam E is recommended when given with clarithromycin. Alternatives to clarithromycin should be considered.

Oral Contraceptives:

Anticonvulsants: Drug interaction studies have not been conducted between Tenolam E and anticonvulsants. When Tenolam E is administered concomitantly with anticonvulsants eg, carbamazepine, phenytoin or phenobarbital there is the potential for reduction in the plasma concentrations of each agent; therefore, periodic monitoring of plasma levels may be required.

Methadone: In a study of HIV-infected IV drug users, co-administration of Tenolam E with methadone resulted in decreased plasma levels of methadone and signs of opiate withdrawal. The methadone dose was increased by a mean of 22% to alleviate withdrawal symptoms. Patients should be monitored for signs of withdrawal and their methadone dose increased as required to alleviate withdrawal symptoms.

St. John's Wort (Hypericum perforatum): Patients on Tenolam E should not concomitantly use products containing St. John's wort (Hypericum perforatum) since it may be expected to result in reduced plasma concentrations of Tenolam E. This effect is due to an induction of CYP3A4 and may result in loss of therapeutic effect and development of resistance.

Antidepressants: There were no clinically significant effects on pharmacokinetic parameters when paroxetine and Tenolam E were co-administered. No dose adjustments are necessary for either Tenolam E of paroxetine when these drugs are co-administered. Sertraline did not significantly alter the pharmacokinetics of Tenolam E. Tenolam E decreased sertraline C_max, C24 and AUC by 28.6-46.3%. The dose of sertraline should be increased when administered with Tenolam E to compensate for the induction of sertraline metabolism by Tenolam E. Sertraline dose increases should be guided by clinical response.

Cetirizine: Cetirizine had no clinically significant effect on Tenolam E pharmacokinetic parameters. Tenolam E decreased cetirizine C_max by 24% but did not alter cetirizine AUC. These changes are not expected to be clinically significant. No dose adjustments are necessary for either Tenolam E or cetirizine when these drugs are co-administered.

Lorazepam: Tenolam E increased lorazepam C_max and AUC by 16.3% and 7.3%, respectively. The pharmacokinetic interaction of Tenolam E on lorazepam is unlikely to be clinically significant. No dose adjustments are necessary for either Tenolam E or lorazepam when these drugs are co-administered.

Cannabinoid Test Interaction: Tenolam E does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been reported in uninfected volunteers who received Tenolam E. False-positive test results have only been observed with the CEDIA DAU Multi-Level THC assay, which is used for screening, and have not been observed with other cannabinoid assays tested including tests used for confirmation of positive results.

See also:
What are the possible side effects of Tenolam E?

The most significant adverse reactions observed in patients treated with Tenolam E are: Psychiatric symptoms; nervous system symptoms; rash.

The most common (>5% in either Tenolam E treatment group) adverse reactions of at least moderate severity among patients in a study treated with Tenolam E in combination with zidovudine/lamivudine or indinavir were rash, dizziness, nausea, headache, fatigue, insomnia and vomiting.

Clinical Trials Experience in Adults: Because clinical studies are conducted under widely varying conditions, the adverse reaction rates reported cannot be directly compared to rates in other clinical studies and may not reflect the rates observed in clinical practice.

Selected clinical adverse reactions of moderate or severe intensity observed in ≥2% of Tenolam E-treated patients in two controlled clinical trials are presented in Table 6 as follows.

Pancreatitis has been reported, although a causal relationship with Tenolam E has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of patients treated with Tenolam E 600 mg than in control patients.

Nervous System Symptoms: For 1008 patients reportedly treated with regimens containing Tenolam E and 635 patients reportedly treated with a control regimen in controlled trials, Table 7 as follow lists the frequency of symptoms of different degrees of severity and gives the discontinuation rates for ≥1 of the following nervous system symptoms: Dizziness, insomnia, impaired concentration, somnolence, abnormal dreaming, euphoria, confusion, agitation, amnesia, hallucinations, stupor, abnormal thinking and depersonalization. The frequencies of specific central and peripheral nervous system symptoms are provided in Table 7.

Psychiatric Symptoms: Serious psychiatric adverse experiences have been reported in patients treated with Tenolam E. In controlled trials, psychiatric symptoms observed at a frequency of >2% among patients treated with Tenolam E or control regimens, respectively, were depression (19%, 16%), anxiety (13%, 9%) and nervousness (7%, 2%).

Rash: For 1008 adults and 57 children reportedly treated with regimens containing Tenolam E and 635 patients treated with a control regimen in controlled trials, the frequency of rash by NCI grade and the discontinuation rates as a result of rash in clinical studies are provided in Table 8 as follows.

As seen in previous table, Table 8 rash is more common in pediatric patients and more often of higher grade (ie, more severe).

Experience with Tenolam E in patients who discontinued other antiretroviral agents of the NNRTI class is limited. Nineteen (19) patients who discontinued nevirapine because of rash have been treated with Tenolam E. Nine (9) of these patients developed mild-to-moderate rash while receiving therapy with Tenolam E and 2 of these patients discontinued because of rash.

Laboratory Abnormalities: Selected grade 3-4 laboratory abnormalities reported in ≥2% of Tenolam E-treated patients in 2 clinical trials are presented in Table 9 as follows.

Patients Co-infected with Hepatitis B or C: Liver function tests should be monitored in patients with a history of hepatitis B and/or C. In the long-term data set from a reported study, 137 patients treated with Tenolam E-containing regimens (median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/or C (hepatitis C antibody positive). Among these co-infected patients, elevations in AST to >5 times ULN developed in 13% of patients in the Tenolam E arms and 7% of those in the control arm, and elevations in ALT to >5 times ULN developed in 20% of patients in the Tenolam E arms and 7% of patients in the control arm. Among coinfected patients, 3% of those treated with Tenolam E-containing regimens and 2% in the control arm discontinued from the study because of liver or biliary system disorders.

Lipids: Increases from baseline in total cholesterol of 10-20% have been observed in some uninfected volunteers receiving Tenolam E. In patients treated with Tenolam E + zidovudine + lamivudine, increases from baseline in nonfasting total cholesterol and HDL of approximately 20% and 25%, respectively, were observed. In patients treated with Tenolam E + indinavir, increases from baseline in nonfasting cholesterol and HDL of approximately 40% and 35%, respectively, were observed. Nonfasting total cholesterol levels ≥240 mg/dL and ≥300 mg/dL were reported in 34% and 9%, respectively, of patients treated with Tenolam E + zidovudine + lamivudine; 54% and 20%, respectively, of patients treated with Tenolam E + indinavir; and 28% and 4%, respectively, of patients treated with indinavir + zidovudine + lamivudine. The effects of Tenolam E on triglycerides and LDL in this study were not well characterized since samples were taken from nonfasting patients. The clinical significance of these findings is unknown.

Clinical Trials Experience in Children: Clinical adverse experiences observed in ≥10% of 57 pediatric patients aged 3-16 years who received Tenolam E capsules, nelfinavir and ≥1 NRTIs in a study were rash (46%), diarrhea/loose stools (39%), fever (21%), cough (16%), dizziness/lightheaded/fainting (16%), ache/pain/discomfort (14%), nausea/vomiting (12%) and headache (11%). The incidence of nervous system symptoms was 18% (10/57). One (1) patient experienced grade 3 rash, 2 patients had grade 4 rash and 5 patients (9%) discontinued because of rash.

Post-Marketing Experience: The following adverse reactions have been identified during post-approval use of Tenolam E. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Allergic reactions, asthenia, redistribution/accumulation of body fat.

Central and Peripheral Nervous System: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paraesthesia, neuropathy, tremor, vertigo.

Endocrine: Gynecomastia.

Gastrointestinal: Constipation, malabsorption.

Cardiovascular: Flushing, palpitations.

Liver and Biliary System: Increased hepatic enzyme, hepatic failure, hepatitis. A few of the post-marketing reports of hepatic failure, including cases in patients with no preexisting hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death.

Metabolic and Nutritional: Hypercholesterolemia, hypertriglyceridemia.

Musculoskeletal: Arthralgia, myalgia, myopathy.

Psychiatric: Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide.

Respiratory: Dyspnea.

Skin and Appendages: Erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome.

Special Senses: Abnormal vision, tinnitus.

Other Reported Adverse events are suicide attempt, suicide ideation, completed suicide, vision blurred.