Pharmacological Treatment Options for HIV/AIDS
Latasha Weeks, PharmD Candidate 2007
Therapeutic Class/AgentsFusion Inhibitors / Therapeutic Class/Agents
Multi-Class Combination Products
Product Availability
Generic (Brand) / § Enfuvirtide, T-20
(Fuzeon ®) / § Efavirenz 600mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg
(Atripla TM)
Mechanism
of Action / General
§ Interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes
Specific
§ Binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein
§ This prevents the conformational changes required for the fusion of viral and cellular membranes / Efavirenz
§ NNRTI – noncompetitive inhibition of HIV-1 reverse transcriptase (RT)
§ HIV-2 RT is not inhibited by efavirenz
Emtricitabine
§ NRTI – competitively inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5’triphosphate
§ Once incorporated into the nascent viral strand, the result is viral DNA chain termination
Tenofovir
§ NtRTI – competitively inhibits activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5’-triphosphate
§ Once incorporated into the nascent viral strand, the result is viral DNA chain termination
EFFICACY
(Indication/Use, Clinical Data Support) / § Indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy
§ Indication is based on results from two 48-week multinational studies (TORO 1 and TORO 2) that examined the efficacy and safety of Fuzeon in combination with other antiretroviral drugs
(per Fuzeon® Drug Monograph) / § Indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults
SAFETY
(Major Drug Interactions,
Pre-cautions, Contra-indications,
Adverse Effects,
Pregnancy Risk Category) / Major Drug Interactions:
§ No significant interactions identified (not an inhibitor of CYP450 enzymes)
Contraindications:
§ Hypersensitivity to enfuvirtide or any of its components
Precautions/Warnings:
§ Monitor closely for signs/symptoms of pneumonia
§ May cause hypersensitivity reactions (rash, fever, nausea, vomiting, hypotension, elevated transaminase)
§ Local injection site reactions may occur
§ Safety and efficacy have not been established in children <6 years of age
Adverse Effects:
§ Insomnia
§ Injection site reactions (pain, erythema, induration, pruritus, nodule or cyst formation)
§ Depression or anxiety
§ Weight loss
§ Triglyceride increase
§ Neuropathy
Pregnancy Risk Category:
§ B / Major Drug Interactions:
§ Should not be administered concurrently with astemizole, cisapride, midazolam, triazolam, or ergot derivatives because competition for CYP3A4 by efavirenz could result in inhibition of metabolism of these drugs and create a potential for serious and/or life-threatening adverse events
§ Should not be administered concurrently with voriconazole because efavirenz significantly decreases voriconazole plasma concentrations
§ Should not be administered concurrently with St. John’s wort because the plasma levels of efavirenz are expected to substantially decrease
§ Should not be administered concurrently with Combivir (lamivudine/zidovudine); Emtriva (emtricitabine); Epivir or Epivir-HBV (lamivudine); Epzicom (abacavir/lamivudine); Trizivir (abacavir/lamivudine/zidovudine); Sustiva (efavirenz); Truvada (emtricitabine/tenofovir); Viread (tenofovir)
Contraindications:
§ Hypersensitivity to any of the components of Atripla
Precautions/Warnings:
§ Treatment with Atripla should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)
§ The safety and efficacy of Atripla have not been established in patients co-infected with HIV and HBV and severe acute exacerbations of HBV have been reported in patients after the discontinuation of emtricitabine and tenofovir, so it is recommended that all patients with HIV be tested for the presence of HBV before initiating antiretroviral therapy
§ Hepatic function should be closely monitored with both clinical and laboratory follow up for at least several months in patients who discontinue Atripla and are coinfected with HIV and HBV.
§ Serious psychiatric adverse experiences have been reported in patients treated with efavirenz (e.g., severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, manic reactions)
§ Persons with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits
Adverse Effects:
§ Nervous System symptoms (dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, hallucinations, euphoria, confusion, agitation, amnesia, stupor, abnormal thinking)
§ Psychiatric symptoms (see Precautions/Warnings)
§ Rash
§ Anxiety
§ Arthralgia
§ Increased cough
§ Dyspepsia
§ Fever
§ Myalgia
§ Pain
§ Abdominal and back pain
§ Peripheral neuropathy
§ Pneumonia
§ Rhinitis
Pregnancy Risk Category:
§ D
Dosage & Administration
(Include renal and/or hepatic adjustments) / Dosage Form:
§ Injection powder for reconstitution – 108mg (90mg/ml following reconstitution with 1.1ml of sterile water)
§ Convenience Kit of 60 single-use vials of 90mg of enfuvirtide, 60 vials of sterile water for injection, 60 reconstitution syringes, 60 administration syringes, and alcohol wipes
Dosage:
§ Adults – 90 mg twice daily
§ Children ≥ 6 years – 2mg/kg twice daily (maximum dose: 90mg twice daily
§ No dosage adjustment required for renal or hepatic impairment
Administration:
§ Must be reconstituted with 1.1ml of sterile water for injection
§ After adding sterile water, the vial should be gently tapped for 10 seconds and then gently rolled between the hands to avoid foaming and to ensure all particles of drug are in contact with the liquid and no drug remains on the vial wall
§ The vial should then be allowed to stand until the powder goes completely into solution, which could take up to 45 minutes / Dosage Form:
§ Tablet – 600mg of efavirenz; 200mg of emtricitabine; 300mg tenofovir
Dosage:
§ Adult – One tablet once daily
§ Children – Not recommended for use in patients <18 years of age
Administration:
§ Take orally on an empty stomach
§ May take at bedtime to improve tolerability of nervous system symptoms
Monitoring
(Efficacy and Toxicity Parameters) / Efficacy:
§ Decrease in viral load
§ Increase in CD4 cell count
Toxicity:
§ Signs/symptoms of injection site reactions (itching, swelling, redness, pain or tenderness, hardened skin, or bumps)
§ Signs/symptoms of bacterial pneumonia
§ Signs/symptoms of allergic reaction (trouble breathing, fever with vomiting and a skin rash, blood in urine, or swelling in the feet) / Efficacy:
§ Decrease in viral load
§ Increase in CD4 cell count
Toxicity:
§ Nervous system symptoms (as described above)
§ Other adverse events (as described above)
Patient Education / Education points on Administration:
§ Once reconstituted, it should be injected immediately or kept refrigerated in the original vial until use
§ Reconstituted enfuvirtide must be used within 24 hours
§ Refrigerated reconstituted solution should be brought to room temperature before injection
§ The vial should be inspected visually to ensure that the contents are fully dissolved in solution and that the solution is clear, colorless, and without bubbles or particulate matter
§ Reconstituted solution should be injected subcutaneously in the upper arm, abdomen or anterior thigh
§ The injection should be given at a site different from the preceding injection site and only where there is no current injection site reaction.
§ Do not inject into moles, scar tissue, bruises, or the navel
Education points on Side Effects:
§ Almost all people get injection site reactions with Fuzeon
§ Reactions are usually mild to moderate, but occasionally may be severe
§ Reactions on the skin where Fuzeon is injected included: itching, swelling, redness, pain or tenderness, hardened skin, or bumps
§ Reactions usually happen within the first week of treatment and can happen again as you keep using the medication
§ The reaction usually lasts for less than 7 days
§ Injection site reactions may be worse when injections are given again in the same place on the body, or when the injection is given deeper than it should be (e.g., in the muscle)
§ If the injection site reaction you are having is severe, call your healthcare provider right away
§ People with HIV are also at a greater risk of getting bacterial pneumonia, as well as getting it more often. Contact your healthcare provider immediately if you have a cough, fever, or trouble breathing
§ You should also contact your healthcare provider immediately if you believe you may be experiencing a serious allergic reaction to the medication (trouble breathing, fever with vomiting and a skin rash, blood in your urine, or swelling of your feet)
Education on Storage:
§ Store at room temperature (77°F)
§ Reconstituted solution should be stored under refrigeration at (36°F to 46°F) and used within 24 hours / Education points on Administration:
§ Take the exact amount of Atripla that your healthcare provider prescribes. Never change the dose on your own. Do not stop taking this medication unless your healthcare provider tells you to stop.
§ You should take your dose on an empty stomach with water
§ Taking Atripla at bedtime may make some side effects less bothersome.
§ Do not miss a dose. If you forget to take the medication, take the missed dose right away, unless it is almost time for your next dose. Do not double the next dose.
§ Tell your healthcare provider if you start any new medications or change how you take old ones. Your doses may need adjustment
Education on Storage:
§ Store this medication at room temperature (77°F)
Cost
(1-month) / § Convenience Kit - $2,452.09 / § 30 tablets - $1,349.98
References
(Guidelines, Drug Info Sources)
Latasha Weeks, PharmD Candidate 2007 Pharmacotherapy Presentation – Pharmaceutical Care Rotation
University of Maryland School of Pharmacy Happy Harry’s Pharmacy Patient Care Center, Perryville, MD