Consumer medicine information

1 Name of Medicine

Cabotegravir and rilpivirine.

2 Qualitative and Quantitative Composition

Cabenuva contains cabotegravir 200 mg/mL (400 mg/2 mL or 600 mg/3 mL) prolonged-release suspension for injection and rilpivirine 300 mg/mL (600 mg/2 mL or 900 mg/3 mL) prolonged-release suspension for injection.
List of excipients with known effect. None.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Cabotegravir prolonged-release suspension for injection is a white to light pink suspension.
Rilpivirine prolonged-release suspension for injection is a white to off-white suspension.

4 Clinical Particulars

4.9 Overdose

There is currently no experience with overdosage of Cabenuva.
There is no specific treatment for overdose with Cabenuva. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Cabotegravir and rilpivirine are known to be highly protein bound in plasma; therefore, dialysis is unlikely to be helpful in removal of cabotegravir or rilpivirine from the body. Management of overdose with Cabenuva should take into consideration the prolonged exposure to the medicine following an injection (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Cabotegravir was not mutagenic or clastogenic using in vitro tests in bacteria and cultured mammalian cells, and an in vivo rodent micronucleus assay.
Rilpivirine has tested negative in the in vitro Ames reverse mutation assay, and in vitro clastogenicity mouse lymphoma assay, tested in the absence and presence of a metabolic activation system. Rilpivirine did not induce chromosomal damage in the in vivo micronucleus test in mice.
Carcinogenicity. Cabotegravir was not carcinogenic in long term oral studies in the mouse and rat at doses resulting in up to 7-8 and 26 times, respectively (75 mg/kg/day in male mice and rats and 35 mg/kg/day in female mice), the maximum AUC in patients.
Rilpivirine was evaluated for carcinogenic potential by oral gavage administration to mice and rats up to 104 weeks. Daily doses of 20, 60 and 160 mg/kg/day were administered to mice and doses of 40, 200, 500 and 1500 mg/kg/day were administered to rats. An increase in the incidences of hepatocellular adenomas and carcinomas was observed in mice and rats. An increase in the incidences of follicular cell adenomas and/or carcinomas in the thyroid gland was observed in rats. Administration of rilpivirine did not cause a statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or rats. The observed hepatocellular findings in mice and rats are considered to be rodent specific, associated with liver enzyme induction. A similar mechanism does not exist in humans; hence, these tumors are not relevant for humans. The follicular cell findings are considered to be rat specific, associated with increased clearance of thyroxine and are not considered to be relevant for humans. At the lowest tested doses in carcinogenicity studies, the systemic exposures (based on AUC) to rilpivirine were > 17 times relative to those observed in humans at the recommended doses (25 mg once daily orally or 600 mg IM injection monthly).

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Cabotegravir. Chemical name: (3S,11aR)-N-[(2,4-Difluorophenyl) methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide.
Molecular formula: C₁₉H₁₇F₂N₃O₅.
Molecular weight: 405.35 g/mol.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSCABOTE.gif CAS number. 1051375-10-0.
Cabotegravir is a white to almost white solid.
Rilpivirine. Chemical name: 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile.
Molecular formula: C₂₂H₁₈N₆.
Molecular weight: 366.42 g/mol.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSRILPIV.gif CAS number. 500287-72-9.
Rilpivirine is a white to off white powder.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/CABENUST.gif