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Information

dolutegravir

doe-loo-teg-ra-veer (Tivicay, Tivicay PD)

FIXED COMBINATION(S)

Dovato: dolutegravir/lamivudine (antiretrovirals): 50 mg/300 mg. Juluca: dolutegravir/rilopivirine (antiretrovirals): 50 mg/25 mg.

Triumaq: dolutegravir/abacavir/lamivudine (antiretrovirals): 50 mg/600 mg/300 mg.

Classification

Uses

Treatment of HIV-1 infection in adults and pediatric pts at least 4 wks of age and weighing at least 3 kg.

Treatment of mild, moderate, or severe dementia of Alzheimer's disease. OFF-LABEL: Treatment of behavioral syndromes in dementia, dementia associated with Parkinson's disease, Lewy body dementia.

Precautions

Contraindications: Hypersensitivity to dolutegravir. Co-administration of dofetilide. Cautions: Diabetes, hepatic/renal impairment, history of hepatitis or tuberculosis, prior hypersensitivity reaction to INSTIs.

Contraindications: History of hypersensitivity to donepezil, other piperidine derivatives. Cautions: Asthma, COPD, bradycardia, bladder outflow obstruction, history of ulcer disease, those taking concurrent NSAIDs, supraventricular cardiac conduction disturbances (e.g., sick sinus syndrome, Wolff-Parkinson-White syndrome), seizure disorder.

Action

Inhibits HIV integrase by blocking strand transfer of retroviral DNA integration (essential for HIV replication cycle). Therapeutic Effect: Interferes with HIV replication, slowing progression of HIV infection.

Reversibly inhibits enzyme acetylcholinesterase, increasing concentration of acetylcholine at cholinergic synapses, enhancing cholinergic function in CNS. Therapeutic Effect: Slows progression of Alzheimer's disease.

Pharmacokinetics

Widely distributed. Metabolized in liver. Peak plasma concentration: 2-3 hrs. Excreted in feces (53%), urine (31%). Half-life: 14 hrs.

Well absorbed after PO administration. Protein binding: 96%. Extensively metabolized. Eliminated in urine, feces. Half-life: 70 hrs.

Lifespan Considerations

Pregnancy/Lactation: May increase risk of neural tube defects when used at conception and in early pregnancy. Breastfeeding not recommend due to risk of postnatal HIV transmission. Unknown if distributed in human breast milk. Children: Safety and efficacy not established in pts less than 4wks or weighing under 3 kg or who are INSTI-experienced with documented or clinically suspected resistance to other INSTIs. Elderly: May have increased risk of adverse effects or worsening hepatic, renal, cardiac function.

Pregnancy/Lactation: Unknown if drug is distributed in breast milk. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: Medications containing aluminum, calcium, magnesium or iron; strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin), nonnucleoside reverse transcriptase inhibitors (e.g., efavirenz, etravirine, nevirapine); protease inhibitors (e.g., fosampre-navir/ritonavir, tipranavir/ritonavir, sucralfate) may decrease concentration/effects. May increase concentration/effect of metformin. HERBAL:St John's wort may decrease therapeutic effect. FOOD: None known. LAB VALUES: May increase serum ALT, AST, bilirubin, cholesterol, creatinine, creatine kinase (CK), glucose, lipase, triglycerides. May decrease creatinine clearance, neutrophils.

DRUG: Anticholinergic agents (e.g., glycopyrrolate, scopolamine) may decrease therapeutic effect. May increase concentration/effects of antipsychotic agents, beta blockers (e.g., atenolol, carvedilol, metoprolol), succinylcholine. HERBAL: None significant. FOOD: None known. LAB VALUES: None significant,

Availability

Tablets: 10 mg, 25 mg, 50 mg. Tablets, Soluble: 5 mg.

Tablets: 5 mg, 10 mg, 23 mg. Tablets (Orally Disintegrating): 5 mg, 10 mg. Transdermal System: patch provides 5 mg/day, 10 mg/day.

Administration/Handling

PO

Soluble tablets:

  • Give without regard to food. Administer at least 2 hrs before or at least 6 hrs after giving medications containing aluminum, calcium, iron, magnesium (supplements, antacids, laxatives). May be dispersed in water as an oral suspension or given whole. Do not administer more than 1 tablet at a time to reduce risk of choking. Do not break, cut, or crush tablets.
PO
  • May be given at bedtime without regard to food.
  • Swallow tablets whole; do not break, crush, dissolve, or divide.
  • Follow dose with water.
TRANSDERMAL

Storage

  • Allow to reach room temperature before opening.
  • Apply to back (avoiding the spine). Do not apply to red, irritated, or cut skin.
  • Refrigerate unused patches. Do not freeze.

Indications/Routes/Dosage

HIV Infection

PO: ADULTS/ELDERLY: Treatment naïve or treatment-experienced, INSTI naïve; virologically suppressed: 50 mg once daily. Increase to 50 mg twice daily if also receiving efavirenz, fosamprenavir/ritonavir, tipranavir/ ritonavir, rifampin or INSTI-experienced with certain INSTI-associated resistance substitutions or clinically suspected IN-STI resistance. INFANTS, CHILDREN, ADOLESCENTS WEIGHING 14 KG OR MORE: Soluble tablets for oral suspension (preferred in pts less than 20 kg): 14-19 KG: 25 mg once daily. 20 KG OR GREATER: 30 mg once daily. Tablets: 14-19 kg: 40 mg once daily. 20 kg or greater: 50 mg once daily. INFANTS AND CHILDREN WEIGHING 3-13 KG: Soluble tablets for oral suspension: 10-13 KG: 20 mg once daily. 6-9 KG: 15 mg once daily. 3-5 KG: 5 mg once daily.

Dosage in Renal Impairment

CrCl 30 mL/min or less: Use caution.

Dosage in Hepatic Impairment

Mild to Severe impairment: No dose adjustment.

Alzheimer's Disease

PO: ADULTS, ELDERLY: For mild to moderate, initially 5 mg/day at bedtime. May increase at 4- to 6-wk intervals to 10 mg/day at bedtime. Range: 5–10 mg/day. For moderate to severe Alzheimer's, a dose of 23 mg once daily can be administered once pt has been taking 10 mg once daily for at least 3 mos. Range: 10–23 mg/day. Transdermal: (apply patch wkly): Initially, 5 mg/day. After 4-6 wks, may increase to 10 mg/day.

Dosage in Renal/Hepatic Impairment

No dose adjustment.

Side Effects

Rare (3%-1%): Insomnia, headache, nausea.

Frequent (11%–8%): Nausea, diarrhea, headache, insomnia, nonspecific pain, dizziness. Occasional (6%–3%): Mild muscle cramps, fatigue, vomiting, anorexia, ecchymosis. Rare (3%–2%): Depression, abnormal dreams, weight loss, arthritis, drowsiness, syncope, frequent urination.

Adverse Effects/Toxic Reactions

Hypersensitivity reaction including rash, fever, angioedema, difficulty breathing, skin blistering/peeling, arthralgia, lethargy was reported. Pts co-infected with hepatitis B or C have increased risk for viral reactivation, worsening of hepatic function, and may experience hepatic decompensation and/or failure if therapy is discontinued. May cause redistribution/accumulation of body fat (lipodystrophy). May induce immune recovery syndrome (inflammatory response to dormant opportunistic infections such as Mycobacterium avium, cytomegalovirus, PCP, tuberculosis, or acceleration of autoimmune disorders such as Graves' disease, polymyositis, Guillain-Barré).

  • NURSING CONSIDERATIONS BASELINE ASSESSMENT Obtain CBC, CMP, CD4+ count, viral load, HIV-1 RNA level; pregnancy test in females of reproductive potential. Screen all pts for hepatitis B or C co-infection. Receive full medication history including herbal products. Offer emotional support. INTERVENTION/EVALUATION Monitor CD4+ count, viral load, HIV-1 RNA level for treatment effectiveness. Monitor LFT; assess for hepatic injury (bruising, hematuria, jaundice, right upper abdominal pain, nausea, vomiting, weight loss). If discontinuation of drug regimen occurs, monitor hepatic function for viral reactivation. Initiate anti-HBV therapy if warranted. Monitor renal function as clinically indicated. An increase of serum creatinine greater than 0.4 mg/dL from baseline may indicate renal impairment. Cough, dyspnea, fever, excess band cells on CBC may indicate acute infection (WBC may be unreliable in pts with uncontrolled HIV infection). Assess skin for skin reactions, rash. Monitor for immune recovery syndrome. PATIENT/FAMILY TEACHING
  • Treatment does not cure HIV infection nor reduce risk of transmission. Practice safe sex with barrier methods or abstinence.
  • Drug resistance can form if treatment is interrupted; do not run out of supply.
  • As immune system strengthens, it may respond to dormant infections hidden within the body. Report fever, chills, body aches, cough, night sweats, shortness of breath.
  • Fatal cases of liver inflammation or failure have occurred; report abdominal pain, clay-colored stools, yellowing of skin or eyes, weight loss.
  • Report symptoms of kidney inflammation or disease (decreased urine output, flank pain, darkened urine); skin reactions (rash, pustules, skin eruptions).
  • Breastfeeding not recommended.
  • Antiretrovirals may cause excess body fat in upper back, neck, breast, trunk, while also causing decreased body fat in legs, arms, face.
  • Do not take newly prescribed medications unless approved by prescriber who originally started treatment.
  • Do not take herbal products, esp. St. John's wort.

donepezil

doe-nep-e-zil

(Adlarity, Aricept RDT , Aricept) Do not confuse Aricept with Aciphex, Ascriptin, or Azilect.

FIXED-COMBINATION(S)

Namzaric: donepezil/memantine (NMDA receptor antagonist): 10 mg/14 mg, 10 mg/28 mg.

CLASSIFICATION

PHARMACOTHERAPEUTIC: Central acetylcholinesterase inhibitor. CLINICAL: Cholinergic.

Overdose may result in cholinergic crisis (severe nausea, increased salivation, diaphoresis, bradycardia, hypotension, flushed skin, abdominal pain, respiratory depression, seizures, cardiorespiratory collapse). Increasing muscle weakness may occur, resulting in death if muscles of respiration become involved. Antidote: Atropine sulfate 1–2 mg IV with subsequent doses based on therapeutic response.

Nursing Considerations

  • BASELINE ASSESSMENT Assess cognitive function (e.g., memory, attention, reasoning). Obtain baseline vital signs. Assess history for peptic ulcer, urinary obstruction, asthma, COPD, seizure disorder, cardiac conduction disturbances. INTERVENTION/EVALUATION Monitor behavior, mood/cognitive function, activities of daily living. Monitor for cholinergic reaction (GI discomfort/cramping, feeling of facial warmth, excessive salivation/diaphoresis), lacrimation, pallor, urinary urgency, dizziness. Monitor for nausea, diarrhea, headache, insomnia. PATIENT/FAMILY TEACHING
  • Report nausea, vomiting, diarrhea, diaphoresis, increased salivary secretions, severe abdominal pain, dizziness.
  • May take without regard to food (best taken at bedtime).
  • Not a cure for Alzheimer's disease but may slow progression of symptoms.