abacavir sulfate and lamivudine

abacavir sulfate and lamivudine

Epzicom, Kavexa (UK)

Pharmacologic class: Nucleoside analogue

Therapeutic class: Antiretroviral agent

Pregnancy risk category C

FDA Boxed Warning

• Give only to patients whose regimens would otherwise include both abacavir sulfate and lamivudine.
• Abacavir component may cause serious and potentially fatal hypersensitivity reactions, including multi-organ syndrome marked by fever, rash, GI distress, malaise, fatigue, achiness, dyspnea, cough, and pharyngitis. Discontinue immediately if you suspect such a reaction. If hypersensitivity can't be ruled out, discontinue permanently, even if other diagnoses are possible.
• After hypersensitivity reaction, never restart drug or other agents containing it, because more severe symptoms (including severe hypotension and death) may arise within hours.
• Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have occurred in patients receiving one or both components.
• Severe acute hepatitis B exacerbations have occurred in patients coinfected with hepatitis B virus and human immunodeficiency virus (HIV) after they discontinued lamivudine.

Action

Abacavir converts to its active metabolite (carbovir triphosphate), and lamivudine is phosphorylated to its active metabolite (lamivudine triphosphate) by intracellular enzymes. These metabolites inhibit activity of HIV-1 reverse transcriptase. Drug interferes with DNA and RNA synthesis, thereby inhibiting viral reproduction.

Availability

Tablets: 600 mg abacavir/300 mg lamivudine

⊘Indications and dosages

➣ HIV-1 infection

Adults: 1 tablet P.O. daily

Contraindications

• Hypersensitivity to abacavir, lamivudine, or other product components
• Hepatic impairment

Precautions

Use cautiously in:
• treatment-experienced patients (cross-resistance may occur)
• concurrent hepatitis B infection
• renal impairment
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

☞ Before administering, ask patient if he's allergic to abacavir or lamivudine.
• Always give in combination with other antiretrovirals.
• Administer with plenty of water, with or without food.
• Know that drug isn't recommended for patients who would require dosage adjustment, because tablet shouldn't be broken.

Route	Onset	Peak	Duration
P.O.	Unknown	Unknown	Unknown

Adverse reactions

CNS: paresthesia, peripheral neuropathy, insomnia, depression or depressed mood, migraine, fatigue, malaise, weakness, dizziness, vertigo, anxiety, abnormal dreams, seizures

GI: nausea, diarrhea, abdominal pain, gastritis, stomatitis, pancreatitis

Hematologic: lymphadenopathy, splenomegaly, anemia (including pure red-cell aplasia and severe anemias progressing with therapy) , aplastic anemia

Hepatic: posttreatment exacerbation of hepatitis B, hepatic steatosis

Metabolic: hyperglycemia, lactic acidosis

Musculoskeletal: muscle weakness, rhabdomyolysis

Respiratory: abnormal breath sounds, wheezing

Skin: alopecia, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome

Other: body fat redistribution, fever, allergic reactions including urticaria and anaphylaxis

Interactions

Drug-drug. Nelfinavir, sulfamethoxazole/trimethoprim: increased lamivudine blood level

Drug-diagnostic tests. Amylase, bilirubin, creatine kinase, glucose, lipase, triglycerides: elevated levels

Liver function tests: abnormal results

Platelet count: decreased

Drug-behaviors. Alcohol use: increased abacavir blood level

Patient monitoring

• Monitor patients (especially women and overweight patients) for signs and symptoms of lactic acidosis.
• Monitor hepatic function closely during therapy and for at least several months afterward.

Patient teaching

☞ Advise patient not to use drug if he is allergic to abacavir or lamivudine.
• Tell patient to take drug with plenty of water, with or without food.
☞ Instruct patient to stop taking drug and get immediate medical attention if he experiences such allergic symptoms as fatigue, general ill feeling, achiness, rash, fever, difficulty breathing, cough, throat inflammation, or severe nausea, vomiting, diarrhea, or abdominal pain.
☞ Caution patient never to take drug again if he experiences an allergic reaction.
• Tell patient to make sure he receives medication guide and warning card issued with each prescription and refill. Teach him to carry card at all times.
☞ Advise patient to contact prescriber right away if he develops symptoms of liver impairment (unusual tiredness, weakness, nausea, itching, yellowing of eyes or skin, tenderness on upper right side of abdomen, or flulike symptoms).
☞ Tell patient not to stop taking drug without consulting prescriber. If he stops taking it for any reason other than allergic reaction, he must consult prescriber before restarting, because serious or life-threatening reactions may occur.
• Tell HIV-infected women not to breastfeed infants, to avoid risk of transmitting HIV infection.
• Inform patient that he'll have regular blood tests during drug therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.