Drug

Dosages

Interactions

For 2 weeks of Abametapir application, avoid taking drugs that are substrates of CYP3A4, CYP2B6 or CYP1A2

Adverse Effects

• Erythema (4%)
• Rash (3.2%)
• Scalp erythema/edema (3.2%)
• Skin burning sensation (2.6%)
• Vomiting (1.7%)
• Contact dermatitis (1.7%)
• Scalp pruritus (1.4%)
• Eye irritation (1.2-1.7%)
• Hair color changes (1%)

Contraindications & Warnings

• Risk of Neonatal Benzyl Alcohol Toxicity: Systemic exposure to benzyl
  alcohol has been associated with serious adverse reactions and death in
  neonates and low birth-weight infants.
• Safety and effectiveness in pediatric patients below the age of 6 months have not been established. Use is not recommended in pediatric patients under 6 months of age because of the potential for increased systemic absorption.
• Risk of Benzyl Alcohol Toxicity from Accidental Ingestion: Administer
  only under direct supervision of an adult.

Safety Advice

🍺   Alcohol: Caution

Pharmacology

Mechanism of Action: Abametapir is a novel pediculicidal metalloproteinase inhibitor. Metalloproteinases have a role in physiological processes critical to egg development and survival of lice

Absorption

• Peak plasma time: 0.57-1.54 hr

Peak plasma concentration

• 6 months to <1 year: 228-418 ng/mL
• 1 to <2 years: 147-209 ng/mL
• 2 to <3 years: 160-206 ng/mL
• 3 to 17 years: 52-121 ng/mL

AUC

• 6 months to <1 year: 688-1057 ng⋅hr/mL
• 1 to <2 years: 406-446 ng⋅hr/mL
• 2 to <3 years: 602-633 ng⋅hr/mL
• 3 to 17 years: 194-330 ng⋅hr/mL

Distribution: Protein-bound Abametapir: 91.3-92.3%, Abametapir carboxyl (metabolite): 96-97.5%

Metabolism: Extensively metabolized, primarily by CYP1A2 to a mono-hydroxylated metabolite (abametapir hydroxyl) and further to a mono-carboxylated metabolite (abametapir carboxyl)

Elimination: Excretion of abametapir and its human metabolites was not examined

Half-life (adults): 21 hr; ~71 hr or longer (abametapir carboxyl)

General Considerations

Inform the patient and caregiver of the following instructions

• Do not ingest.
• Keep out of reach of children. 

Use in Specific Populations

• Avoid contact with eyes.
• Wash hands after application.
• Hair may be shampooed any time after the treatment.
• Treatment with abametapir involves a single application. Do not re-treat.
• Discard any unused portion. Do not flush contents down sink or toilet.

Dosages

Interactions

Contraindicated

• apixaban
• artemether/lumefantrine
• cariprazine
• cobimetinib
• dienogest/estradiol valerate
• elbasvir/grazoprevir
• elvitegravir/cobicistat/emtricitabine/tenofovir DF
• lumacaftor/ivacaftor
• lumefantrine
• lurasidone
• mifepristone
• naloxegol
• ombitasvir/paritaprevir/ritonavir & dasabuvir
• panobinostat
• praziquantel
• regorafenib
• rilpivirine
• roflumilast
• vandetanib

Serious

• abemaciclib
• acalabrutinib
• adenovirus types 4 and 7 live, oral
• aldesleukin
• anthrax vaccine
• apalutamide
• apremilast
• axicabtagene ciloleucel
• axitinib
• BCG vaccine live
• bedaquiline
• bosutinib
• brigatinib
• cabozantinib
• carbamazepine
• ceritinib
• chloramphenicol
• cimetidine
• clarithromycin
• cobicistat
• copanlisib
• dabrafenib
• dihydroergotamine
• dihydroergotamine intranasal
• diphtheria & tetanus toxoids/ acellular pertussis vaccine
• diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine
• dronedarone
• eliglustat
• elvitegravir
• erdafitinib
• ergotamine
• erythromycin base
• erythromycin ethylsuccinate
• erythromycin lactobionate
• erythromycin stearate
• ethinylestradiol
• everolimus
• hepatitis A vaccine inactivated
• hepatitis a/b vaccine
• hepatitis a/typhoid vaccine
• hepatitis b vaccine
• human papillomavirus vaccine, nonavalent
• human papillomavirus vaccine, quadrivalent
• ibrutinib
• idelalisib
• influenza virus vaccine quadrivalent
• influenza virus vaccine quadrivalent, intranasal
• influenza virus vaccine trivalent
• influenza virus vaccine trivalent, adjuvanted
• ivabradine
• ivacaftor
• ivosidenib
• ixazomib
• Japanese encephalitis virus vaccine
• ketoconazole
• lasmiditan
• lovastatin
• macimorelin
• macitentan
• measles (rubeola) vaccine
• measles mumps and rubella vaccine, live
• measles, mumps, rubella and varicella vaccine, live
• meningococcal A C Y and W-135 polysaccharide vaccine combined
• midostaurin
• naldemedine
• nefazodone
• neratinib
• netupitant/palonosetron
• nivolumab
• olaparib
• osimertinib
• palbociclib
• perampanel
• pneumococcal vaccine 13-valent
• pneumococcal vaccine heptavalent
• pneumococcal vaccine polyvalent
• ponatinib
• quinidine
• rabies vaccine
• rabies vaccine chick embryo cell derived
• ranolazine
• rifabutin
• rifampin
• rolapitant
• romidepsin
• rotavirus oral vaccine, live
• rubella vaccine
• silodosin
• simeprevir
• simvastatin
• sirolimus
• smallpox (vaccinia) vaccine, live
• sofosbuvir/velpatasvir
• sonidegib
• squill
• St John’s Wort
• testosterone intranasal
• tetanus toxoid adsorbed or fluid
• tezacaftor
• tick borne encephalitis vaccine
• tisagenlecleucel
• tofacitinib
• tolvaptan
• trabectedin
• travelers diarrhea and cholera vaccine inactivated
• tucatinib
• typhoid polysaccharide vaccine
• typhoid vaccine live
• ulipristal
• valbenazine
• varicella virus vaccine live
• vemurafenib
• venetoclax
• vorapaxar
• voxelotor
• yellow fever vaccine
• zoster vaccine live

Monitor Closely

• abiraterone
• aceclofenac
• acemetacin
• albiglutide
• alitretinoin
• almotriptan
• alprazolam
• amiodarone
• amobarbital
• antithrombin alfa
• antithrombin III
• aprepitant
• argatroban
• aripiprazole
• armodafinil
• artemether/lumefantrine
• aspirin
• aspirin rectal
• aspirin/citric acid/sodium bicarbonate
• atazanavir
• atorvastatin
• atracurium
• avanafil
• bazedoxifene/conjugated estrogens
• belatacept
• bemiparin
• benzhydrocodone/acetaminophen
• bexarotene
• bivalirudin
• bortezomib
• bosentan
• bosutinib
• brentuximab vedotin
• brexpiprazole
• budesonide
• buprenorphine
• buprenorphine buccal
• buprenorphine subdermal implant
• buprenorphine, long-acting injection
• buspirone
• butabarbital
• butalbital
• calcifediol
• carbamazepine
• celecoxib
• cenobamate
• cholera vaccine
• cholestyramine
• choline magnesium trisalicylate
• cilostazol
• cinacalcet
• ciprofloxacin
• cisatracurium
• clarithromycin
• clopidogrel
• clotrimazole
• clozapine
• colchicine
• conivaptan
• conjugated estrogens
• conjugated estrogens, vaginal
• corticorelin
• cortisone
• crizotinib
• crofelemer
• cyclosporine
• dabrafenib
• dalteparin
• darifenacin
• darunavir
• dasatinib
• deferasirox
• dengue vaccine
• denosumab
• DHEA, herbal
• diazepam
• dichlorphenamide
• diclofenac
• diflunisal
• diltiazem
• doxorubicin
• doxorubicin liposomal
• dronabinol
• dronedarone
• duvelisib
• efavirenz
• elagolix
• eletriptan
• eliglustat
• elvitegravir/cobicistat/emtricitabine/tenofovir DF
• encorafenib
• enoxaparin
• erlotinib
• erythromycin base
• erythromycin ethylsuccinate
• erythromycin lactobionate
• erythromycin stearate
• eslicarbazepine acetate
• estradiol
• estradiol vaginal
• estrogens conjugated synthetic
• estrogens esterified
• estropipate
• ethotoin
• etodolac
• etoposide
• etravirine
• eucalyptus
• exemestane
• exenatide injectable solution
• exenatide injectable suspension
• fedratinib
• felodipine
• fenbufen
• fenoprofen
• fentanyl
• fentanyl intranasal
• fentanyl transdermal
• fentanyl transmucosal
• fesoterodine
• fingolimod
• flibanserin
• fluconazole
• fludrocortisone
• flurbiprofen
• fondaparinux
• fosamprenavir
• fosphenytoin
• fostamatinib
• gefitinib
• gemifloxacin
• glecaprevir/pibrentasvir
• glycerol phenylbutyrate
• grapefruit
• griseofulvin
• guanfacine
• haemophilus influenzae type b vaccine
• hemin
• heparin
• hydrocodone
• hydrocortisone
• hydroxyprogesterone caproate
• ibuprofen
• ibuprofen IV
• ifosfamide
• iloperidone
• indacaterol, inhaled
• indinavir
• indomethacin
• influenza A (H5N1) vaccine
• influenza virus vaccine (H5N1), adjuvanted
• influenza virus vaccine quadrivalent, recombinant
• influenza virus vaccine trivalent, recombinant
• insulin degludec
• insulin degludec/insulin aspart
• insulin inhaled
• irinotecan
• irinotecan liposomal
• isoniazid
• istradefylline
• itraconazole
• ivacaftor
• ixabepilone
• ketoconazole
• ketoprofen
• ketorolac
• ketorolac intranasal
• lapatinib
• letermovir
• levofloxacin
• levonorgestrel intrauterine
• levonorgestrel oral
• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
• liraglutide
• lomitapide
• lopinavir
• loratadine
• lornoxicam
• lovastatin
• lumefantrine
• maraviroc
• marijuana
• meclofenamate
• medroxyprogesterone
• mefenamic acid
• meloxicam
• meningococcal group B vaccine
• mestranol
• methadone
• methylprednisolone
• metronidazole
• miconazole vaginal
• midazolam
• mitotane
• modafinil
• moxifloxacin
• nabumetone
• naproxen
• nefazodone
• nelfinavir
• nevirapine
• nicardipine
• nifedipine
• nilotinib
• nisoldipine
• ocrelizumab
• ofloxacin
• olodaterol inhaled
• ondansetron
• ospemifene
• oxaprozin
• oxcarbazepine
• oxiconazole
• oxycodone
• ozanimod
• paclitaxel
• paclitaxel protein bound
• pancuronium
• parecoxib
• pazopanib
• pentobarbital
• phenindione
• phenobarbital
• phenytoin
• pimavanserin
• piroxicam
• poliovirus vaccine inactivated
• pomalidomide
• ponatinib
• posaconazole
• prednisolone
• prednisone
• primidone
• protamine
• quercetin
• quetiapine
• quinidine
• quinupristin/dalfopristin
• ranolazine
• repaglinide
• ribociclib
• rifampin
• rifapentine
• riociguat
• ritonavir
• rivaroxaban
• rocuronium
• rufinamide
• salicylates (non-asa)
• salsalate
• saquinavir
• sarecycline
• secobarbital
• selexipag
• sildenafil
• simvastatin
• sipuleucel-T
• sirolimus
• sodium picosulfate/magnesium oxide/anhydrous citric acid
• sodium sulfate/potassium sulfate/magnesium sulfate
• sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol
• solifenacin
• somatrem
• sorafenib
• spironolactone
• St John’s Wort
• stiripentol
• succinylcholine
• sulfasalazine
• sulindac
• sunitinib
• suvorexant
• tacrolimus
• tadalafil
• tamoxifen
• tasimelteon
• tazemetostat
• tecovirimat
• temsirolimus
• theophylline
• ticagrelor
• tinidazole
• tipranavir
• tofacitinib
• tolfenamic acid
• tolmetin
• tolterodine
• tolvaptan
• topiramate
• toremifene
• tramadol
• trastuzumab
• trastuzumab deruxtecan
• trazodone
• triamcinolone acetonide injectable suspension
• triazolam
• tucatinib
• ubrogepant
• vardenafil
• vecuronium
• vemurafenib
• verapamil
• vilazodone
• voriconazole
• vortioxetine
• warfarin
• xipamide
• zafirlukast
• zoster vaccine recombinant

Minor

• acarbose
• albendazole
• alfentanil
• alfuzosin
• alosetron
• ambrisentan
• amitriptyline
• amlodipine
• amphotericin B deoxycholate
• armodafinil
• aspirin
• aspirin rectal
• aspirin/citric acid/sodium bicarbonate
• atazanavir
• balsalazide
• bendroflumethiazide
• bosentan
• bumetanide
• calcium acetate
• calcium carbonate
• calcium chloride
• calcium citrate
• calcium gluconate
• caspofungin
• cevimeline
• chlorothiazide
• chlorpropamide
• chlorthalidone
• choline magnesium trisalicylate
• chromium
• clarithromycin
• clomipramine
• colestipol
• cyclopenthiazide
• cyclosporine
• danazol
• dapsone
• desipramine
• diflunisal
• disopyramide
• docetaxel
• donepezil
• dutasteride
• efavirenz
• eplerenone
• esomeprazole
• ethacrynic acid
• eucalyptus
• feverfew
• finasteride
• fluoxymesterone
• furosemide
• galantamine
• glimepiride
• glipizide
• glyburide
• hydrochlorothiazide
• imatinib
• imipramine
• indapamide
• insulin aspart
• insulin detemir
• insulin glargine
• insulin glulisine
• insulin lispro
• insulin NPH
• insulin regular human
• isoniazid
• isradipine
• ketoconazole
• lansoprazole
• mesalamine
• mesterolone
• metformin
• methyclothiazide
• methyltestosterone
• metolazone
• metyrapone
• miglitol
• montelukast
• nateglinide
• nimodipine
• nitrendipine
• omeprazole
• oxandrolone
• oxybutynin
• oxymetholone
• paclitaxel
• paclitaxel protein bound
• pantoprazole
• parecoxib
• pimozide
• pioglitazone
• porfimer
• propafenone
• quinine
• rabeprazole
• ramelteon
• repaglinide
• rosiglitazone
• salicylates (non-asa)
• salsalate
• sargramostim
• saxagliptin
• sitagliptin
• somatropin
• sufentanil
• sulfasalazine
• tacrolimus
• testosterone
• testosterone buccal system
• testosterone topical
• tolazamide
• tolbutamide
• torsemide
• troleandomycin
• vesnarinone
• vildagliptin
• vinblastine
• vincristine
• vincristine liposomal
• vinorelbine
• willow bark
• zaleplon
• ziprasidone
• zolpidem
• zonisamide

Adverse Effects

• Allergic reactions: Anaphylactoid reaction, anaphylaxis, angioedema
• Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, edema, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis
• Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria
• Endocrine: Decreased carbohydrate and glucose tolerance, development of the cushingoid state, hyperglycemia, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients
• Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention, tumor lysis syndrome
• Gastrointestinal: Abdominal distention, elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis
• Metabolic: Negative nitrogen balance due to protein catabolism
• Musculoskeletal: Aseptic necrosis of femoral and humeral heads, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures
• Neurological/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo
• Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, vision blurred
• Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain

Warnings

Contraindications

• Systemic fungal infection
• Documented hypersensitivity
• Cerebral malaria
• Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids

Cautions

• Use with caution in cirrhosis, diverticulitis, myasthenia gravis, peptic ulcer disease, ulcerative colitis, renal insufficiency, pregnancy
• Average and large doses of corticosteroids can cause elevation of blood pressure, sodium and water retention, and increased excretion of potassium; these effects are less likely to occur with synthetic derivatives except when used in large doses; dietary salt restriction and potassium supplementation may be necessary; all corticosteroids increase calcium excretion
• Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with potential for glucocorticosteroid insufficiency after withdrawal of treatment; adrenocortical insufficiency may result from too rapid withdrawal; may be minimized by gradual reduction of dosage; relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, reinstitute hormone therapy; if patient is receiving steroids already, may increase dosage
• Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients; changes in thyroid status of patient may necessitate adjustment in dosage
• May exacerbate systemic fungal infections
• Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, toxoplasma; rule out latent amebiasis or active amebiasis before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea
• Use with great care in patients with known or suspected Strongyloides (threadworm) infestation; corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia; not for use in cerebral malaria
• Close observation necessary if corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity; reactivation of the disease may occur; during prolonged corticosteroid therapy, these patients should receive chemoprophylaxis
• Use of oral corticosteroids not recommended in treatment of optic neuritis and may lead to increase in risk of new episodes; corticosteroids should not be used in active ocular herpes simplex
• Use lowest possible dose to control condition under treatment; risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used
• May lead to inhibition of bone growth in pediatric patients and development of osteoporosis at any age; special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy
• Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations; existing emotional instability or psychotic tendencies may also be aggravated by corticosteroids
• Thromboembolic disorders
• Myopathy has been reported
• Delayed wound healing
• If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated; if exposed to measles, prophylaxis with immune globulin (IG) may be indicated; if chickenpox develops, treatment with antiviral agents should be considered
• Latent tuberculosis may be reactivated (patients with positive tuberculin test should be monitored)
• Some suggestion (not fully substantiated) of slightly increased cleft palate risk if corticosteroids are used in pregnancy
• Prolonged corticosteroid use may result in elevated intraocular pressure, glaucoma, or cataracts with possible damage to optic nerves, and may enhance establishment of secondary ocular infections due to bacteria, fungi, or viruses; consider referral to ophthalmologist for patients who develop ocular symptoms or use corticosteroid-containing products for more than 6 weeks
• Prolonged therapy has been associated with development of Kaposi sarcoma
• May affect velocity growth in children; monitor routinely
• Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy in physiologic doses (eg, for Addison’s disease)

Epidural injection

• Serious neurologic events, some resulting in death, have been reported with epidural injection
• Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke
• These serious neurologic events have been reported with and without use of fluoroscopy
• Safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use

Drug interaction overview

• Strong CYP3A4 inhibitors: Coadministration of strong and moderate CYP3A4 inhibitors increased dexamethasone exposure, which may increase the risk of adverse reactions
• Strong CYP3A4 inducers: Coadministration of strong CYP3A4 inducers may decrease dexamethasone exposure, which may result in loss of efficacy
• Cholestyramine: Cholestyramine may increase clearance of corticosteroids and potentially decrease corticosteroid exposure
• Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hr before initiating corticosteroid therapy
• Ephedrine: Ephedrine may decrease dexamethasone exposure and may result in loss of efficacy. Consider increasing the dexamethasone dose when used with ephedrine
• Estrogens: Estrogens may decrease the hepatic metabolism of certain corticosteroids and increase exposures, which may increase the risk of adverse reactions
• CYP3A4 substrates: Coadministration of dexamethasone with substrates may decrease the concentration of these drugs, resulting in loss of efficacy of these drugs
• Oral anticoagulants: Coadministration of anticoagulants with corticosteroids may reduce the response to anticoagulants; frequently monitor coagulation indices to maintain the desired anticoagulant effect
• Amphotericin B injection and potassium-depleting agents: Sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroid; closely monitor potassium levels
• Antidiabetics: Corticosteroids may increase blood glucose concentrations; consider adjusting the dose of antidiabetic agents, as necessary
• Isoniazid: Serum concentrations of isoniazid may be decreased with corticosteroids
• Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use
• Digitalis glycosides: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia
• Nonsteroidal Anti-Inflammatory Agents (NSAIDS): Concomitant use of aspirin (or other NSAIDS) and corticosteroids increases the risk of gastrointestinal side effects; clearance of salicylates may be increased with concurrent use of corticosteroids; monitor for toxicity
• Phenytoin: Reports of both increases and decreases in phenytoin levels with dexamethasone coadministration, leading to alterations in seizure control
• Vaccines: Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, defer routine administration of vaccines or toxoids until therapy is discontinued
• Concomitant therapies that may increase the risk of thromboembolism: Erythropoietic agents, or other agents that may increase the risk of thromboembolism, such as estrogen containing therapies, coadministered with dexamethasone may increase the risk of thromboembolism; monitor for risk of thromboembolism
• Thalidomide: Toxic epidermal necrolysis has been reported with concomitant use of thalidomide. Closely monitor for toxicity
• Skin tests: Corticosteroids may suppress reactions to skin tests

Safety Advice

🍺   Alcohol: Caution

Pharmacology

Mechanism of Action: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes (PMNs) and reducing capillary permeability; stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines; suppresses lymphocyte proliferation through direct cytolysis, inhibits mitosis, breaks down granulocyte aggregates, and improves pulmonary microcirculation

Absorption

Onset: Between a few minutes and several hours; dependent on indication and route of administration

Peak serum time: 8hr (IM); 1-2 hr (PO)

Distribution: Vd: 2 L/kg

Metabolism: Metabolized in liver

Elimination: Half-life: 1.8-3.5 hr (normal renal function)

Excretion: Urine (mainly), feces (minimally)

Report an error

Dosages

Interactions

Contraindicated

• Enzalutamide
• Carbamazepine
• Phenytoin
• Rifampin
• MitotaneSt John’s wort (Hypericum perforatum)

Serious

• Grazoprevir
• Voxilaprevir

Monitor Closely

• Ethinyl estradiol
• Rosuvastatin
• Atorvastatin
• Fluvastatin
• Pitavastatin
• Simvastatin

Adverse Effects

• Nausea 10%
• Diarrhoea 4%
• Headache 4%
• Abdominal pain 3%
• Dyspepsia 3%
• Fatigued 3%
• Rash 3%
• Sleep disturbance 3%
• Immune Reconstitution Inflammatory Syndrome 2%
• Somnolence 2%
• Vomiting 2%
• Elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection: Elevations in hepatic transaminases were observed in a greater proportion of subjects with HBV and/or HCV co-infection compared with those with HIV mono-infection.
• Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: The concomitant use of fostemsavir and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to 1) Loss of therapeutic effect of fostemsavir and possible development of resistance due to reduced exposure of temsavir 2) Possible prolongation of QTc interval from increased exposure to temsavir.

Less common adverse reactions

• Cardiac Disorders: Electrocardiogram QT prolonged, Torsade de Pointes
• Musculoskeletal Disorders: Myalgia.
• Nervous System Disorders: Dizziness, dysgeusia, neuropathy peripheral (includes pooled terms: neuropathy peripheral and peripheral sensory neuropathy).
• Skin and Subcutaneous Tissue Disorders: Pruritus.

Contraindications & Warnings

Immune Reconstitution Syndrome

• Immune reconstitution syndrome has been reported in patients. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
• Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment

QTc Prolongation

• Seen with higher than recommended dosages at 2,400 mg twice daily, 4 times the recommended daily dose, has been shown to significantly prolong the QTc interval of the electrocardiogram

Safety Advice

🍺   Alcohol: Caution

Pharmacology

Mechanism of Action

• Fostemsavir tromethamine is a prodrug of temsavir is a first-in-class HIV-1 attachment inhibitor. After oral administration, fostemsavir is converted to temsavir, which is then absorbed and exerts antiviral activity by attaching directly to the glycoprotein 120 (gp120) subunit on the surface of the virus, thereby blocking HIV from attaching to host immune system CD4+ T-cells and preventing the virus from infecting those cells and multiplying. As fostemsavir is the first antiretroviral therapy to target this step of the viral cycle, there is no demonstrated resistance to other classes of antiretrovirals, which may help patients who have become resistant to most other medicines.

About Temsavir

• Temsavir  is a substrate of CYP3A, esterases, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
• Coadministration of fostemsavir with drugs that are strong CYP3A inducers result in decreased concentrations of temsavir.
• Coadministration of fostemsavir with drugs that are moderate CYP3A inducers and/or strong CYP3A, P-gp and/or BCRP inhibitors are not likely to have a clinically relevant effect on the plasma concentrations of temsavir. Temsavir is an inhibitor of OATP1B1 and OATP1B3.

Pharmacokinetic properties of Temsavir

• Absolute bioavailability: 26.9%
• Distribution: Plasma protein binding 88.4%
• Major route of elimination: Metabolism
• Half-life: 11 hours
• Metabolic pathwayse: Hydrolysis (esterases) [36.1% of oral dose], Oxidation (CYP3A4) [21.2% of oral dose], UGT [<1% of oral dose]
• Excretion: Urine (unchanged drug) 51 %, feces (unchanged drug) 33%, bile 5%

General Considerations

• Advise the patient to read the FDA-approved patient labeling (Patient Information).
• Hypersensitivity Reactions
• Immune Reconstitution Syndrome: Advice patients to inform their healthcare provider immediately of any signs and symptoms of
  infection, as inflammation from the previous infection, may occur soon after combination antiretroviral therapy, including when fostemsavir is started
• QTc Interval Prolongation: Advise patients that it may produce changes in their electrocardiogram (i.e., QT prolongation). Instruct patients to consult their healthcare provider if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness
• Patients with Hepatitis B or C Virus Co-infection: Advise patients that it is recommended to have laboratory testing and to take medications for
  HBV or HCV as prescribed
• Drug Interactions: Fostemsavir may interact with other drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products,
  including St. John’s wort
• Pregnancy Registry: Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to fostemsavir during pregnancy.
• Instruct mothers with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk
• Potential Odor of Tablets: Tablets may have a slight vinegar-like odour
• Missed Dosage: Advise patients to avoid missing doses as it can result in the development of resistance. Instruct patients that if they miss a dose of fostemsavir, to take it as soon as they remember. Advise
  patients not to double their next dose or take more than the prescribed dose

General Monitoring Parameters

• ECG for estimation of QT interval
• CBC at baseline with periodic tests for liver function, renal function, blood glucose level
• CD4 count

Dosages

Interactions

Contraindicated

• lefamulin

Serious

• adalimumab
• alefacept
• alfuzosin
• amiodarone
• amitriptyline
• amoxapine
• anakinra
• anthrax vaccine
• antithymocyte globulin equine
• antithymocyte globulin rabbit
• apomorphine
• arformoterol
• arsenic trioxide
• artemether/lumefantrine
• asenapine
• azathioprine
• azithromycin
• basiliximab
• BCG vaccine live
• bedaquiline
• canakinumab
• chlorpromazine
• ciprofloxacin
• cisapride
• citalopram
• clarithromycin
• clofazimine
• clomipramine
• clozapine
• crizotinib
• cyclosporine
• dapsone topical
• dasatinib
• degarelix
• desipramine
• deutetrabenazine
• digoxin
• diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine
• disopyramide
• dofetilide
• dolasetron
• dronedarone
• droperidol
• encorafenib
• entrectinib
• eribulin
• erythromycin base
• erythromycin ethylsuccinate
• erythromycin lactobionate
• erythromycin stearate
• escitalopram
• etanercept
• everolimus
• ezogabine
• flecainide
• fluconazole
• fluoxetine
• fluphenazine
• formoterol
• foscarnet
• gemifloxacin
• gemtuzumab
• glasdegib
• glatiramer
• golimumab
• haloperidol
• hepatitis A vaccine inactivated
• hepatitis a/b vaccine
• hepatitis a/typhoid vaccine
• hepatitis b vaccine
• human papillomavirus vaccine, nonavalent
• human papillomavirus vaccine, quadrivalent
• ibutilide
• iloperidone
• indacaterol (Inhaled)
• indapamide
• infliximab
• influenza virus vaccine quadrivalent
• influenza virus vaccine quadrivalent, intranasal
• influenza virus vaccine trivalent
• inotuzumab
• isradipine
• Japanese encephalitis virus vaccine
• lapatinib
• leflunomide
• levofloxacin
• lofexidine
• lopinavir
• maprotiline
• measles (rubeola) vaccine
• measles mumps and rubella vaccine, live
• measles, mumps, rubella and varicella vaccine, live
• mefloquine
• meningococcal A C Y and W-135 polysaccharide vaccine combined
• methadone
• mifepristone
• moxifloxacin
• muromonab CD3
• mycophenolate
• nilotinib
• nortriptyline
• octreotide
• ofloxacin
• olanzapine
• ondansetron
• osimertinib
• paliperidone
• panobinostat
• pasireotide
• pazopanib
• pentamidine
• perphenazine
• pimavanserin
• pimozide
• pitolisant
• pneumococcal vaccine 13-valent
• pneumococcal vaccine heptavalent
• pneumococcal vaccine polyvalent
• posaconazole
• procainamide
• propafenone
• protriptyline
• quetiapine
• quinidine
• quinine
• rabies vaccine
• rabies vaccine (chick embryo cell derived)
• ranolazine
• remdesivir
• ribociclib
• rilonacept
• rilpivirine
• risperidone
• ritonavir
• romidepsin
• rotavirus oral vaccine, live
• rubella vaccine
• saquinavir
• sertraline
• sirolimus
• smallpox vaccine (live)
• solifenacin
• sorafenib
• sotalol
• sunitinib
• tacrolimus
• telavancin
• temsirolimus
• tetanus toxoid adsorbed or fluid
• tetrabenazine
• thioridazine
• thiothixene
• tick borne encephalitis vaccine
• tocilizumab
• tofacitinib
• tongkat ali
• toremifene
• travelers diarrhea and cholera vaccine inactivated
• trimipramine
• typhoid polysaccharide vaccine
• typhoid vaccine live
• ustekinumab
• vandetanib
• vardenafil
• varicella virus vaccine live
• vemurafenib
• vilanterol/fluticasone furoate inhaled
• voriconazole
• vorinostat
• yellow fever vaccine
• ziprasidone
• zoster vaccine live

Monitor Closely

• astragalus
• cholera vaccine
• dengue vaccine
• denosumab
• echinacea
• influenza virus vaccine quadrivalent, recombinant
• influenza virus vaccine trivalent, recombinant
• maitake
• mercaptopurine
• methotrexate
• osilodrostat
• ozanimod
• selpercatinib
• siponimod
• sipuleucel-T
• tobramycin inhaled
• zoster vaccine recombinant

Minor

• chloroquine
• praziquantel

Adverse Effects

Frequency Not Defined

• Blood and lymphatic system disorders: Bone marrow failure, anemia, aplastic anemia, agranulocytosis, leukopenia, and thrombocytopenia; hemolysis reported in individuals with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency
• Cardiovascular disorders: Cardiomyopathy, QT interval prolongation, and ventricular arrhythmias and torsade de pointes
• Ear and labyrinth disorders: Vertigo, tinnitus, nystagmus, nerve deafness, deafness
• Eye disorders: Irreversible retinopathy with retinal pigmentation changes (bull’s eye appearance), visual field defects (paracentral scotomas) and visual disturbances (visual acuity), maculopathies (macular degeneration), decreased dark adaptation, color vision abnormalities, corneal changes (edema and opacities) including corneal deposition of drug with or without accompanying symptoms (halo around lights, photophobia, blurred vision)
• Gastrointestinal disorders: Nausea, vomiting, diarrhea, abdominal pain
• Hepatobiliary disorders: Liver function tests abnormal, Acute hepatic failure
• Immune system disorders: Urticaria, angioedema, bronchospasm
• Metabolism and nutrition disorders: Decreased appetite, hypoglycemia, porphyria, weight decreased
• Musculoskeletal and connective tissue disorders: Sensorimotor disorder, skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups, depression of tendon reflexes and abnormal nerve conduction
• Nervous system disorders: Headache, dizziness, seizure, ataxia and extrapyramidal disorders such as dystonia, dyskinesia, tremor
• Psychiatric disorders: Affect/emotional lability, nervousness, irritability, nightmares, psychosis, suicidal behaviour
• Skin and subcutaneous tissue disorders: Rash, pruritus, pigmentation disorders in skin and mucous membranes, hair color changes, alopecia; dermatitis bullous eruptions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, dermatitis exfoliative, acute generalized exanthematous pustulosis (AGEP)

Contraindications & Warnings

Contraindicated in

• Hypersensitivity to HCQ and related components
• Long-term use in children
• Retinal or visual field changes due to similar compounds
• Pre-existing cardiomyopathy and cardiac rhythm disorders
• G6PD deficiency

Increased risk for

• QT prolongation
• Exacerbation of psoriasis
• Retinal damage
• Loss of visual acuity
• Exacerbation of porphyria
• Dermatitis outbreaks
• Cardiomyopathy
• Aplastic anaemia
• Agranulocytosis
• Myopathy
• Suicidal behaviour
• In patients with cardiovascular disorders
• In patients with hepatic and renal impairment
• In concomitant use with antidiabetic agent

Safety Advice

🍺   Alcohol: Caution

Pharmacology

Mechanism of Action

• In Malaria: HCQ interfere with the digestive vacuole function within susceptible malarial parasites by increasing pH and interrupting with the lysosomal degradation of Hb, thereby impeding the normal cell function of sensitive parasites
• In COVID-19: The antiviral activity of HCQ in COVID-19 might be exerted by changing the pH at the cell membrane surface and inhibiting viral fusion. It can also inhibit nucleic acid replication, glycosylation of viral proteins, as well as viral assembly and release
• In Rheumatoid arthritis and systemic lupus erythematosus: Mechanisms underlying the anti-inflammatory and immunomodulatory effects of hydroxychloroquine are unknown

Pharmacokinetic

• Bioavailability: Variable (74% on average); Tmax = 2–4.5 hours
• Protein binding: 45%
• Metabolism: Liver
• Elimination half-life: 32–50 days
• Excretion: Mostly kidney (23–25% as unchanged drug), also biliary (<10%)

Pharmacodynamics

• Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia. 
• Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements

General Considerations

• Advise patients to take with food or milk
• Alcohol must be avoided
• Toxicity: Patients experiencing an overdose may present with headache, drowsiness, visual disturbances, cardiovascular collapse, convulsions, hypokalemia, rhythm and conduction disorders including QT prolongation, torsades de pointes, ventricular tachycardia, and ventricular fibrillation. This may progress to sudden respiratory and cardiac arrest. Overdose should be treated with immediate gastric lavage and activated charcoal at a dose of at least 5 times the hydroxychloroquine dose within 30 minutes. Parenteral diazepam may be given to treat cardiotoxicity, transfusion may reduce serum concentrations of the drug, patients should be monitored for at least 6 hours, fluids should be given, and ammonium chloride should be given to acidify urine and promote urinary excretion. Patients may also be given epinephrine. Patients with severe toxicity should be intubated and sedated with high doses of benzodiazepines, and circulatory support should be provided with fluids and vasopressors (e.g. epinephrine). Consider early intravenous lipid therapy for patients with ventricular dysrhythmias or hypotension. Orotracheal intubation for airway protection should be performed early in cases of severe psychomotor agitation, repeated seizure activity, coma, or evidence of severe quinidine-like cardiotoxicity

General Monitoring Parameters

• ECG for estimation of QT interval
• CBC at baseline with periodic tests for liver function, renal function, blood glucose level, and muscle strength during long-term therapy 
• Ophthalmologic examination

Dosages

Interactions

Contraindicated

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

Serious

• ganciclovir
• ribavirin
• valganciclovir

Monitor Closely

• atazanavir
• cabozantinib
• didanosine
• efavirenz
• emtricitabine
• enfuvirtide
• fosamprenavir
• indinavir
• lamivudine
• methadone
• nelfinavir
• nevirapine
• orlistat
• ritonavir
• saquinavir
• stavudine
• tenofovir DF
• tipranavir
• zidovudine

Minor

• ethanol

Adverse Effects

10%

• Nausea (17-19%)
• Headache (9-13%)
• Malaise/Fatigue (12%)
• Nausea & vomiting (10%)

1-10%

• Hypersensitivity reaction (2-8%)
• Diarrhea (5-7%)
• Musculoskelatal pain (5-7%)
• Hypertriglyceridemia (6%)
• Hepatic: AST Increased (6%)
• Depression (4-6%)
• Fever/chills (3-6%)
• Viral respiratory infections (5%)
• Ear/nose /throat infections (4-5%)
• Rash (4-5%)
• Anxiety (3-5%)
• Thrombocytopenia (1%)

<1%

• Anaphylactoid reaction
• Pulmonary hypertension
• Erythema multiforme
• Redistribution/accumulation of body fat
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Pancreatitis
• GGT increased
• Hepatic steatosis
• Heptaomegaly
• Hepatotoxicity
• Lactic acidosis
• MI

Black Box Warnings

• Prior hypersensitivity reaction to abacavir
• Presence of HLA-B*5701 allele
• Moderate or severe hepatic impairment

Safety Advice

Pharmacology

Mechanism of Action: Guanosine analogue that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which in turn inhibits viral replication

General Considerations

• Hypersensitivity reaction to Abacavir usually occur within 9 days of starting abacavir; ~ 90% occur within 6 weeks, although these reactions may occur at any time during therapy.
• These hypersensitivity reactions to Abacavir usually include signs or symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (e.g. pharyngitis, dyspnea, cough), and GI symptoms (e.g. abdominal pain, diarrhoea, nausea, vomiting). Other signs and symptoms include lethargy, headache, myalgia, oedema, abnormal chest x-ray findings, arthralgia and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis and death have occurred in association with hypersensitivity reactions.
• Physical findings (lymphadenopathy, erythema multiforme, mucous membrane lesions and rash [maculopapular, urticarial or variable]) and laboratory abnormalities (e.g. elevated liver function tests, elevated creatine phosphokinase, elevated creatinine and lymphopenia) may occur.
• Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status.
• Abacavir should not be restarted because more severe symptoms may occur within hours, including life-threatening hypotension and death.

General Monitoring Parameters

• CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, serum transaminases, triglycerides, serum amylase 
• HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status 
• Signs and symptoms of hypersensitivity 

Practice Insights

• Do not re-challenge patients who have experienced hypersensitivity to Abacavir regardless of HLA-B*5701 status.
• Abacavir is always used as a combination drug.
• Abacavir is contraindicated in infants less than 90 days.
• Meta-analysis has failed to show a causal association between Abacavir and myocardial infarction so far.
• Meta-analysis has shown that Abacavir related toxicity is manageable and can be safely used as first or second-line antiretroviral therapy especially in the population where HLA B5701 is rare (as in sub-Saharan Africa)