Dapivirine

Registered South African indications:

• Human immunodeficiency virus type 1 (HIV-1) infection risk reduction

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Women with unknown or positive HIV status

Cautions

• Pregnancy
• Breastfeeding
• Elderly
• Unrecognised lower genital tract infections
• Vaginal practices, including dry sex practices
• Menses 
• Non-adherence to product use
• Clinical symptoms consistent with an acute viral infection and recent (<1 month) exposure to HIV-1 is suspected
• Concomitant tampon use
• Tampon removal
• Coadministration with vaginally administered agents
• Coadministration with vaginal antimicrobials e.g clotrimazole, miconazole, metronidazole and clindamycin
• Coadministration with vaginal rings including contraceptive vaginal rings
• Coadministration  with vaginal diaphragms

Forms avail. in SA and covered in this monograph: vri

Human immunodeficiency virus type 1 (HIV-1) infection risk reduction
- HIV-uninfected women in combination with safer sex practices when oral pre-exposure prophylaxis (PrEP) is not/cannot be used or is not available

• Vaginal (vri): 1 vaginal ring, inserted and kept in until replaced every 28 days with a new ring

To maintain efficacy, a new ring should be inserted immediately after the previous ring is removed

Time to onset of risk reduction after initial insertion or following reinsertion after the ring has been expelled or removed and not immediately replaced, is unknown. Dapivirine vaginal ring should only be used as part of an overall HIV-1 infection prevention strategy, including the use of other HIV-1 prevention measures, which include consistent and correct condom use and regular testing for other sexually transmitted infections

Used locally in the vagina and only reduces the risk of HIV-1 infection in women by vaginal intercourse

Should not be removed prior to, during or after vaginal sexual intercourse

Each dapivirine vaginal ring contains 25mg of dapivirine and releases approximately 4mg of dapivirine over a period of one month

Not established for use in children below 18 years

Pregnancy

• Caution
• There are no or limited amount of data (less than 300 pregnancy outcomes) from the use in pregnant women
• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity that are relevant to use of the dapivirine vaginal ring
• Although safety has not been established in pregnancy, the benefits of treatment should be considered for pregnant women at high risk of HIV infection, considering the subsequent risk of HIV transmission to the unborn child

Breastfeeding

• Caution 
• Dapivirine has been shown to be excreted in human milk. In one clinical study, dapivirine concentrations in breast milk from sixteen HIV-1 negative mothers who were lactating but not breastfeeding were 70% higher than in maternal plasma. However, since milk concentrations remained low (<1420pg/ml), infant exposure to dapivirine is anticipated to be low (below 1μg/day)
• No formal studies have been conducted in women who are breastfeeding
• There is insufficient information on the effects of dapivirine in newborns/infants
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from use of the dapivirine vaginal ring. The benefit of breastfeeding for the child and the benefit of reducing the risk of HIV-1 infection for the mother should be taken into account

Fertility

• There are no clinical data on the effect of the dapivirine vaginal ring on fertility
• There are no data from animal fertility studies with vaginal administration of dapivirine
• Oral studies in rats have shown effects on fertility but only at exposure levels well in excess of maximum exposure resulting from human vaginal administration, indicating that this is of little relevance to use of the dapivirine vaginal ring

Renal Impairment 

• No dose adjustment recommended 

Hepatic Impairment

• No dose adjustment recommended 

Elderly 

• Caution; no information available

Drugs in Sport

• Permitted - No warnings

Gastrointestinal Disorders

• Lower abdominal pain
• Abdominal discomfort

Genitourinary Disorders

• Urinary tract infection
• Vaginal discharge 
• Vulvovaginal pruritus 
• Vulvovaginitis 
• Pelvic pain 
• Cervicitis
• Cystitis
• Dysuria
• Pollakiuria
• Bladder pain
• Micturition urgency
• Vaginal odour
• Cervix erythema
• Vulvovaginal discomfort
• Vulvovaginal pain
• Cervical discharge
• Cervix ecchymosis
• Pelvic discomfort
• Vaginal erosion
• Cervix oedema
• Uterine cervical erosion
• Cervix petechia
• Genital itching
• Genital discomfort
• Vulval abrasion
• Vaginal laceration
• Vaginal spotting
• Vaginal ecchymosis

Others

• Suprapubic pain
• Application site discomfort
• Application site pain

• Vaginaly administered agents metabolised by CYP450 enzymes  
• Vaginaly administered agents metabolised by UGT enzymes

• HIV-negative status (frequent intervals e.g. at least every 3 months)

Additional observations

• Clinical symptoms consistent with acute viral infection
• Genital infections

Post-menopausal women

• One clinical trial evaluated the mean dapivirine plasma concentration in post-menopausal women aged 45–65 years
• The mean dapivirine plasma concentrations in these women were comparable to the mean dapivirine plasma concentrations in women of reproductive age

Other special populations

• Clinical data suggest that dapivirine vaginal fluid and plasma concentrations were within the same range in black and caucasian women

Dapivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with potent antiviral activity against human immunodeficiency virus type 1 (HIV-1) infection. It prevents viral replication by binding directly to HIV-1 reverse transcriptase and blocking its activity. Dapivirine binding is non-competitive against both the RNA template and the nucleotide substrate. 

Vaginal ring 25mg

• DapiRing (LeBasi)