HIV/AIDS

NRTI (AZT, zidovudine)

Dose: DONT NEED TO KNOW

• S/E: Bone marrow suppression, granulocytopenia, anemia, nausea, vomiting, dizziness, myalgias, headaches, fatigue.
• (late S/E ~6mo) Mitochondial toxicity, lipoatrophy

DI: Zerit® (D4T, stavudine)

NRTI (ddI, didanosine)

• Dose:
• Wt >60kg 400mg QDay
• Wt <60kg 250mg QDay

• S/E: Pancreatitis (primary), peripheral neuropathy, nausea, vomiting, myalgia, fatigue, leukopenia.
• (late S/E ~60mo) Mitochondrial toxicity, lipoatrophy

DI: Viread® (tenofovir), Zerit® (D4T, stavudine)

NRTI (D4T, stavudine)

• Dose:
• Wt >60kg 40mg BID
• Wt<60kg 30mg BID
• Dose to renal function

• S/E: Pancreatitis (primary), peripheral neuropathy, nausea, vomiting, myalgia, fatigue, increase LFTs.
• (late S/E ~6mo) Mitochondrial toxicity, lipoatrophy

DI: Retrovir® (AZT, zidovudine), Videx® (ddI, didanosine)

NRTI (3TC, lamivudine)

Dose: DONT NEED TO KNOW

S/E: Pancreatitis (secondary), increases LFTs

Do not combine with emtricitabine, products too similar

Very well tolerated

NRTI (emtricitabine)

Dose: DONT NEED TO KNOW

S/E: Headache, nausea, diarrhea, rash, black spots on skin (small)

Very well tolerated

NRTI (abacavir)

Dose: DONT NEED TO KNOW

S/E: Hypersensitivity reaction

Well tolerated

• Hypersensitivity reaction:
• Fever
• Rash
• GI (N/V/D, or abdominal pain)
• Constiutional (Malaise, Fatigue)
• Respiratory (Cough)

Less common in African Americans

If patient develops hypersensitivity reaction- STOP drug and NEVER restart.

HLA-B5701 Testing. HLA-B5701 positive patients likely to have Hypersensitivity Reaction (60%)

NtRTI (tenofovir)

• Dose: DONT NEED TO KNOW
• S/E: Increased LFTs, GI, potentially long term renal

• DI:
• Videx® (ddI, didanosine)-Increased AUC, Cmax and Cmin
• Reyataz® (atazanavir)-Decreased AUC, Cmax and Cmin

• AZT (zidovudine) Retrovir®
• d4t (stavudine) Zerit®
• ddI (didanosine) Videx®

Symptoms: Nausea, abdominal dyscomfort, vague feeling of wrongness

Lab abnormalities: Increased Lactic Acid

Supportive Therapy: folate, bicarbonate, I-carnitine, B-vitamines, Co-enzyme Q)

• AZT (zidovudine) Retrovir®
• d4t (stavudine) Zerit®
• ddI (didanosine) Videx®

(zidovudine/lamivudine)

(abacavir/lamivudine/zidovudine)

(abacavir/lamivudine)

(emtricitabine/tenofovir)

NNRTI (nevirapine)

Dose: DONT NEED TO KNOW

S/E: Major S/E is rash, can be severe or life-threatening rashes (SJS). Other important S/E include fever, nausea, H/A, and abnormal liver functions tests.

DI: nevirapine induces CYP3A4 enzymes, must adjust dose of protease.

NNRTI (delavirdine)

Dose: DONT NEED TO KNOW

S/E: Major S/E is rash, can be severe or life-threatening rashes (SJS). Other important S/E include fever, nausea, H/A, and abnormal liver functions tests.

DI: delavirdine inhibits CYP3A4 enzymes, must adjust dose of protease.

NNRTI (efavirenz)

Dose: DONT NEED TO KNOW

• S/E: CNS increased dreams, hung over feeling, tiredness, rash. Worsen depression.
• For people with amphetamine history- "manic" symptoms
• Increased triglycerides, lipodystrophy possible

• DI: Cytochrome CYP3A4 mixed agent.
• Do not give with Ergots, Will decrease concentration of protease inhibitors.
• Avoid midazolam, flurazepam, triazolam.
• Do not give in pregnancy

• NNRTI (rilpivirine)
• Indicated for NAIVE HIV patients
• Category B pregnancy

Dose: DONT NEED TO KNOW

• S/E: Insomnia, Rash, H/A, Depression. All less than efavirenz
• Take with food.

• DI: Cytochrome CYP3A4 substrate
• Do not give with PPIs, carbamazepine, phenobarbital, phenytoin, dexamethasone, St. John's Wort, rifampin, rifabutin
• Give with care Antacids, H2RA

• NNRTI (etravirine)
• 2^nd gen NNRTI. Usable when resistrance exists to efavirenz or nevirapine
• Must take with food.
• Category B Pragnancy: risk vs benefit

Dose: DONT NEED TO KNOW

S/E; Rash, nausea, vomiting, abdominal pain

(efavirenz, emtricitabine, tenofovir)

(rilpivirine, emtricitabine, tenofovir)

Protease inhibitors block the activity of the viral protease enzyme which stops the processing of the gag-pol polyprotein precursor. This leads to the production of non-infectious immature HIV particles.

Should use in combination with anti-retroviral medications for optimal effect

PI (saquinavir)

Dose: DONT NEED TO KNOW

Metabolism: In liver via CYP3A4

• S/E: Nausea, flushing diarrhea, heartburn, increased LFTs, bloating, hyperlipidemia.
• Lypodystrophy, hyperglycemia.

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, ergots, rifampin, lovastatin, or triazolam.

PI (ritonavir)

Dose: DONT NEED TO KNOW

Metabolism: In liver via CYP3A4

S/E: abdominal pain, asthenia, H/A, diarrhea, anorexia, nausea, vomiting, bloating, hyperlipidemia, hyperglycemia, circumoral paresthesis, somnolence, and taste perversion lipodystrophy.

Ritonavir should NOT be given with Alprazolam, amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide, estazolam, flecainide, flurazepam, lovastatin, meperidine, midazolam, piroxicam, propafenone, propoxyphene, quinidine, rifampin, terfenadine, or triazolam.

Ritonavir may increase the AUC of medications metabolized by CYP3A4

PI (indinavir)

Must be taken on an empty stomach, 1 hr prior or 2 hrs after eating, preferably with a low fat diet.

Protein binding 60%. the drug is metabolized by the liver in the P-450 enzymes, but the metabolites are inactive.

Dose: DONT NEED TO KNOW

Metabolism: In liver via CYP3A4

S/E: nephrolithiasis, increases in bilirubin (jaundice), bloating, nausea, vomiting, renal dysfunction (long-term). Hyperglycemia, lipodystrophy, hyperlipidemia

• DI: Should not be given with astemizole, cisapride,
• ketoconazole, lovastatin, midazolam,
• rifampin, terfenadine or triazolam.

Rifabutin doses must be decreased to 150mg daily. Crix dose to 1000 – 1200mg Q8h

PI (nelfinavir)

Best result when taken with a meal.

Metabolized by the liver via CYP2D6 enzymes. Approved for use in children.

Dose: DONT NEED TO KNOW

S/E: Diarrhea, nausea, bloating.

• DI: Should not be given with
• astemizole, cisapride, ketoconazole,
• midazolam, rifampin, terfenadine or triazolam.

PI (lopinavir/ritonavir)

Take with food.

Metabolized by Liver CYP3A4.

Dose: DONT NEED TO KNOW

S/E: Abdominal pain, diarrhea, nausea, vomiting, bloating, hyperlipidemia, reflux, paresthesia (oral).

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, rifampin, terfenadine or triazolam.

PI (atazanavir)

Take with food.

Metabolized by Liver CYP3A4.

Dose: DONT NEED TO KNOW

S/E: Abdominal pain, bloating, reflux, hyperbilirubinemia/jaundice, increased PR interval.

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, rifampin, terfenadine or triazolam. Must boost dose of Atazanavir if given with Tenofovir.

Do not give with PPIs, space H2 antagonists 12 hours.

PI (fosamprenavir)

Take with food.

Metabolized by Liver CYP3A4.

Dose: DONT NEED TO KNOW

S/E: Nausea, headache, rash, bloating.

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, rifampin, terfenadine or triazolam.

PI (tipranavir)

Take with food.

Metabolized by Liver CYP3A4, Inducer.

Dose: DONT NEED TO KNOW

S/E: Abdominal pain, diarrhea, nausea, vomiting, bloating, hyperlipidemia, reflux

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, rifampin, terfenadine or triazolam.

Need to avoid incombination with other PI’s due to effect on their metabolism.

PI (darunavir)

Take with to food.

Metabolized by Liver CYP3A4

Dose- DONT NEED TO KNOW

S/E: VERY MILD abdominal pain, diarrhea, nausea, vomiting, bloating, hyperlipidemia.

DI: Should not be given with astemizole, cisapride, ketoconazole, midazolam, rifampin, terfenadine or triazolam.

Fusion Inhibitor (enfuvirtide)

Dose: 90mg Subq bid

S/E: Injections site reactions

• Must reconstitute, time consuming. Store reconstituted for
• 12 hours refrigerated.

Fusion Inhibitor (maraviroc)

Dose: Heavily dependent on 3A4 for metabolism

• S/E: Rash (to SJS), systemic allergic reactions,
• hepatitis (Black Box).
• Myalgias, dizziness, abdominal pain. ?Cough, fever, URTI.

DI: CYP3A

• Integrase inhibitors (raltegravir)
• glucuronidation metabolized

DO NOT USE WITH RIFAMPIN

Dose: DONT NEED TO KNOW

S/E: Well tolerated. Nausea, diarrhea, anxiety.

DI: rifampin