Consumer medicine information

1. Why am I taking JULUCA?

JULUCA contains the active ingredients dolutegravir and rilpivirine. JULUCA is used to treat human immunodeficiency virus (HIV) infection.
For more information, see Section 1. Why am I taking JULUCA? in the full CMI.

2. What should I know before I take JULUCA?

Do not use if you have ever had an allergic reaction to JULUCA or any of the ingredients listed at the end of the CMI.
Do not use JULUCA if you are taking any of the following medicines: dofetilide, pilsicainide, fampridine, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampicin, rifapentine, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, dexamethasone and products containing St John's wort.
Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I take JULUCA? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with JULUCA and affect how it works.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take JULUCA?

• The usual dosage of JULUCA is one tablet once a day with a meal.

• If you taken certain other medications this will affect when you can take JULUCA.

• Swallow the tablet whole with a glass of water.

5. What should I know while taking JULUCA?

6. Are there any side effects?

Side effects that have been reported include headache, dizziness, nausea, vomiting, stomach pains or discomfort, diarrhoea, increased wind (flatulence), decreased appetite, weight gain, depression, anxiety, difficulty sleeping or falling asleep (insomnia), abnormal dreams, sleep disorders, fatigue, a lack of energy, feeling drowsy, itching, joint pain and muscle pain.
Serious side effects include allergic reactions, suicidal thoughts and behaviours and liver failure. Urgent medical attention is required.
For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

1 Name of Medicine

Dolutegravir (as dolutegravir sodium) and rilpivirine (as rilpivirine hydrochloride).

2 Qualitative and Quantitative Composition

Juluca film-coated tablets contain 50 mg of dolutegravir (as dolutegravir sodium) and 25 mg of rilpivirine (as rilpivirine hydrochloride).
Dolutegravir sodium is a white to light yellow powder and is slightly soluble in water. The partition coefficient (log P) for dolutegravir sodium is 2.2 and the pKa is 8.2.
Rilpivirine hydrochloride is a white to off-white powder. Rilpivirine hydrochloride is practically insoluble in water over a wide pH range, its pKa is 5.6 (pyrimidine moiety) and log P between 1-octanol and a phosphate solution (pH 7.0) is 4.86 (at 21°C).
Juluca tablets also contain: mannitol and lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Pink, film-coated, oval, biconvex tablets debossed with 'SV J3T' on one side.

4 Clinical Particulars

4.9 Overdose

Symptoms and signs. Experience with overdose of Juluca, or the individual components, dolutegravir and rilpivirine is limited.
Treatment. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
There is no specific treatment for overdose with Juluca. If overdose occurs, the patient should be treated supportively with appropriate monitoring, vital signs, ECG (QT interval), and observation of the clinical status of the patient, as necessary. As dolutegravir and rilpivirine are highly bound to plasma proteins, it is unlikely they will be significantly removed by dialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Dolutegravir 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, in vitro chromosomal aberration assay in human lymphocyte 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. No carcinogenicity studies have been conducted with the combination of dolutegravir/rilpivirine.
In long-term oral carcinogenicity studies conducted with dolutegravir no drug-related increases in tumour incidence were found in mice at doses up to 500 mg/kg/day (20 times the human systemic exposure based on AUC at the maximum recommended dose of 50 mg QD) or in rats at doses up to 50 mg/kg/day (17 times the human systemic exposure based on AUC at the maximum recommended dose).
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 1,500 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 tumours 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 the carcinogenicity studies, the systemic exposures (based on AUC) to rilpivirine were 21-fold (mice) and 3-fold (rats), relative to those observed in humans at the recommended dose (25 mg once daily).

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Dolutegravir. The chemical (IUPAC) name for dolutegravir sodium is Sodium (4R,12aS)-9-{[(2,4-difluorophenyl)methyl]carbamoyl}-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate.
Molecular formula: C₂₀H₁₈F₂N₃NaO₅.
Molecular weight of 441.36 g/mol.
Rilpivirine. The chemical name of rilpivirine hydrochloride is 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile monohydrochloride.
Molecular formula: C₂₂H₁₈N₆.HCl.
Molecular weight of 402.88 g/mol.
Chemical structure. The structural formula of dolutegravir sodium is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDOLUTE.gif The structural formula of rilpivirine hydrochloride is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSRILHYD.gif CAS number. 1051375-19-9 (dolutegravir sodium); 700361-47-3 (rilpivirine hydrochloride).

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes

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