1. General Pharmacology of Hydroxychloroquine. 2. Treatment in General. 3. Treatment in Dermatology. 4. Treatment trials for Coronavirus.

1. Pharmacology of Hydroxychloroquine
The 4-aminoquinolines are a family of compounds
derived from quinine, a naturally occurring alkaloid
originally procured from the South American
cinchona bark tree.

2. MECHANISM OF ACTION
Pharmacology of Hydroxychloroquine
Decrease T-cell release of interleukin (IL)-1, IL-6, tumor necrosis
factor-α, and interferon-γ.
Inhibition of toll-like receptor (TLR) 9 family receptors.
(TLRs are intracytoplasmic receptors whose activation of the innate
immune system in response to microbial peptides induces a
significant inflammatory response)

3. MECHANISM OF ACTION
Pharmacology of Hydroxychloroquine
It is concentrated in the Plasmodium (falciparum) digestive vacuole
and prevent polymerization of toxic heme released during
proteolysis of hemoglobin.
Lipophilic weak bases that pass through plasma membranes in their
protonated state, become trapped, and accumulate inside acidic
vesicles such as lysosomes, accounting for their effects in
Plasmodium

4. PROPERTIES & PHARMACOKINETICS
Pharmacology of Hydroxychloroquine
Bitter, water-soluble, and readily absorbed from the GIT with a
relatively good bioavailability, achieving peak concentrations within
8–12 hours
Efficacy is generally seen after 1–3 months of use, but it may take up
to 3–6 months to achieve maximum clinical efficacy. After this time,
the dose may be tapered to a minimum effective dose

5. DOSING & MONITORING
Pharmacology of Hydroxychloroquine
Usual starting doses for HCQ are between 200 and 400 mg/day
Initiation of therapy and maintenance dosing may be different for
each disease
Evaluation of G6PD enzyme, complete blood cell count, and serum
chemistry panel should be performed before initiation of therapy in
all patients
A rigorous laboratory monitoring protocol must be established, as
adverse hematologic and metabolic side effects have been reported
with the use of these medications
Baseline evaluation by an ophthalmologist is necessary. Slit-lamp
assessment, fundoscopic examination, and assessment of visual
acuity and fields should be included.
American Academy of Ophthalmology recommend a dose ≤5
mg/kg/day
Complete blood count performed monthly for 3 months to evaluate
for the presence of hemolytic (or, less commonly, aplastic) anemia.
Liver enzymes should be monthly checked for 3 months, then every
4–6 months thereafter, particularly in those patients who are taking
hepatotoxic medications and in those patients with porphyria.

6. SIDE EFFECTS
Pharmacology of Hydroxychloroquine
 Gastrointestinal: anorexia, nausea, vomiting, diarrhea, weight
loss, and less commonly hepatotoxicity
 Hematologic: hemolytic anemia (glucose-6-phosphate
dehydrogenase deficiency), aplastic anemia, agranulocytosis,
pancytopenia
 Mucocutaneous: pigmentation—blue gray, rashes (urticaria,
morbilliform, lichenoid, exfoliative dermatitis, acute generalized
exanthematous pustulosis), pruritus, worsening psoriasis
 Ophthalmologic: neuromuscular eye toxicity (diplopia, blurred
vision (in high dosing), loss of accommodation), corneal deposits
(halos around lights, photophobia), retinopathy (pre-
maculopathy—reversible and true retinopathy—irreversible)
 Neuromuscular: nightmares, vertigo, tinnitus, nervousness,
irritability, toxic psychosis, seizures, neuromyotoxicity,
myasthenia-like syndrome, ototoxicity, rhabdomyolysis
 High doses: cardiovascular toxicities, hypotension, neurotoxicity,
respiratory or cardiac arrest, death.. Management of overdose
consists of
 gastric lavage,
 ventilation, and
 inotropic support

7. SIDE EFFECTS
Pharmacology of Hydroxychloroquine
 Blue-black cutaneous discoloration (10%-30%) for a prolonged
course. The shins, face, hard palate, and nail beds are most
commonly affected.
 Stevens-Johnson syndrome has also been reported in a patient
treated with HCQ.
 Premaculopathy (reversible retinopathy) or true retinopathy
(irreversible) doses >5 mg/kg/day are believed to decrease the
risk of a true retinopathy

8. DRUG INTERACTIONS
Pharmacology of Hydroxychloroquine
 Penicillamine, Metoprolol, and digoxin levels may be increased
with concurrent use of HCQ
 Smoking decreases efficacy of antimalarial drugs by inducing the
cytochrome P450 system
PRECAUTIONS
 Consider weight for dosing children
 Relatively contraindicated in pregnancy (congenital defects are
rare)
 Use in breastfeeding is relatively contraindicated (HCQ are
excreted in breast milk)
 G6PD deficiencies are susceptible to HCQ-induced hemolytic
anemia and reversible leucopenia

9. INDICATIONS
Hydroxychloroquine General Indications
1955 FDA approved for treatment of malaria and rheumatoid
arthritis
• MALARIA
Acute treatment:
800 mg PO, then 400 mg PO 6-8
hours later, then 400 mg PO at
24 and 48 hours
Prophylaxis:
400 mg PO weekly, starting 2
weeks before exposure and
continued for 4 weeks after
departure from area
• RHEUMATOID ARTHRITIS
400-600 mg PO daily for 4-12
weeks;
maintenance: 200-400 mg PO
daily

10. INDICATIONS
Hydroxychloroquine General Indications
• SYSTEMIC LUPUS ERYTHEMATOSUS
400 mg PO once or twice daily;
maintenance: 200-400 mg PO daily
• PORPHYRIA CUTANEA TARDA (Off-label)
100-200 mg PO 2-3 times/wk

11. INDICATIONS
Hydroxychloroquine in Dermatology

12. CUTANEOUS LUPUS ERYTHEMATOSUS
Hydroxychloroquine in Dermatology
since the 1930s
70% response rate
Widespread, hypertrophic and verrucous lesions, and longstanding
discoid lesions do not respond
Fever, renal, or hematologic abnormalities seen in systemic lupus
erythematosus typically do not respond to antimalarial therapy, but
fatigue, arthralgias, myalgias, serositis, and mucosal ulcerations do
respond to therapy
mucosal ulcerations, calcinosis cutis, lupus panniculitis, and
photosensitivity, lupus panniculitis specifically has been reported to
respond well
onset of action is typically 4–8 weeks; after which time, one may
consider adding or changing therapies

13. POLYMORPHOUS LIGHT ERUPTION
Hydroxychloroquine in Dermatology
Chloroquines decrease IL-1 and -6 and release and absorb UVA light
Topical sunscreens should also be used in conjunction with
antimalarial therapy.
SARCOIDOSIS
6-month course
Suppressive rather than curative
Block antigen processing and presentation to CD-4+ T cells, thus
inhibiting granuloma formation
2-3 mg/kg/day has been reported as being effective

14. CUTANEOUS DERMATOMYOSITIS
Hydroxychloroquine in Dermatology
Effective for amyopathic dermatomyositis
200 mg bid (less than 5 mg/kg/day)
ORAL LICHEN PLANUS
200–400 mg/day

15. CHRONIC ULCERATIVE STOMATITIS
Hydroxychloroquine in Dermatology
complete response to antimalarial therapy lasting for several
months to years.
These medications are now considered first-line therapy for this rare
condition
MISCELLANEOUS
Antimalarials have been reported to be useful in cases of
epidermolysis bullosa, eosinophilic fasciitis, atopic dermatitis, solar
urticaria, scleroderma, urticarial vasculitis, and reticular
erythematous mucinosis, and Sjögren syndrome

16. Updated: Mar 20, 2020
https://www.livescience.com/chloroquine-coronavirus-treatment.html
Hydroxychloroquine in COVID-19
President Donald Trump had declared chloroquine and
hydroxychloroquine as treatments for the novel coronavirus,
claiming that the medications have "gone through the approval
process"
But the U.S. FDA did not approved’em as treatments for COVID-19.
The disease is caused by the coronavirus SARS-CoV-2. Both drugs
must still be assessed in clinical trials before being declared a safe
and effective COVID-19 treatment. Doctors in the U.S. have wide
latitude to prescribe drugs "off-label," meaning for conditions
beyond their initial FDA approval.
It could prevent the spread of the SARS-CoV virus, which caused
severe acute respiratory syndrome nearly 20 years ago

17. Updated: Mar 20, 2020
https://www.livescience.com/chloroquine-coronavirus-treatment.html
Hydroxychloroquine in COVID-19
interferes with the virus's ability to replicate in two ways:
1. The drug enters compartments called endosomes within the cell
membrane. Endosomes tend to be slightly acidic, but the chemical
structure of the drug makes the compartments more basic. Many
viruses, including SARS-CoV, acidify endosomes in order to breach
the cell membrane, release their genetic material and begin
replication; chloroquine blocks this critical step.
2. It prevents SARS-CoV from plugging into a receptor angiotensin-
converting enzyme 2, (ACE2), on primate cells, according to the 2005
report. When the virus inserts its spike protein into the ACE2
receptor, it sets off a chemical process that alters the structure of
the receptor and allows the virus to infect. An adequate dose of
chloroquine appears to undermine this process, and in turn, viral
replication in general, the authors noted.
"It was thought that whatever pertained to SAR-CoV-1 might apply
to SARS-CoV-2," Horovitz said.

18. Updated: Mar 20, 2020
https://www.livescience.com/chloroquine-coronavirus-treatment.html
Hydroxychloroquine in COVID-19
In February, a research group led by virologist Manli Wang of the
Chinese Academy of Sciences put the idea to the test and found that
chloroquine successfully stopped the spread of SARS-CoV-2 in
cultured human cells. Preliminary reports from China, South Korea
and France suggest that the treatment is at least somewhat
effective in treating human patients, and some hospitals in the U.S.
have begun administering the drug.