DELSTRIGO 100 mg/300 mg/245 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Delstrigo 100mg/300mg/245mg film-coated tablets

doravirine/lamivudine/tenofovir disoproxil

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Delstrigo and what is it used for
2. What you need to know before you take Delstrigo
3. How to take Delstrigo
4. Possible side effects
5. Storage of Delstrigo
6. Contents of the pack and other information

1. What is Delstrigo and what is it used for

What is Delstrigo

Delstrigo is used to treat HIV infection (Human Immunodeficiency Virus). It belongs to a group of medicines called antiretrovirals.

Delstrigo contains the active substances:

• Doravirine - a non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Lamivudine - a nucleoside reverse transcriptase inhibitor (NRTI)
• Tenofovir disoproxil - a nucleoside reverse transcriptase inhibitor (NRTI)

What Delstrigo is used for

Delstrigo is used to treat HIV infection in adults and adolescents from 12 years of age and weighing at least 35 kg. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). You should not take Delstrigo if your doctor has told you that the virus causing your infection is resistant to any of the medicines contained in Delstrigo.

How Delstrigo works

Delstrigo works by preventing HIV from producing more viruses in your body through:

• reducing the amount of HIV in the blood (this is called “viral load”)
• increasing the number of white blood cells called “CD4+ T cells”. This can strengthen your immune system and reduce the risk of early death or acquiring infections because your immune system is weak.

2. What you need to know before you take Delstrigo

Do not takeDelstrigo

• if you are allergic to doravirine, lamivudine, or tenofovir disoproxil or any of the other ingredients of this medicine (listed in section 6).
• if you are taking any of the following medicines:

• carbamazepine, oxcarbazepine, phenobarbital, phenytoin (medicines to treat seizures)
• rifampicin, rifapentine (medicines to treat tuberculosis)
• St. John's Wort (Hypericum perforatum, a herbal remedy used for depression and anxiety) or products that contain it
• mitotane (a medicine to treat cancer)
• enzalutamide (a medicine to treat prostate cancer)
• lumacaftor (a medicine to treat cystic fibrosis)

Do not take Delstrigo if you are in any of the above situations. If you are unsure, consult your doctor, pharmacist, or nurse before taking Delstrigo. Also, see the list in the section "Other medicines and Delstrigo".

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Delstrigo.

Severe skin reactions

Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, have been reported in patients treated with Delstrigo. Stop taking Delstrigo and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Worsening of hepatitis B infection

If you have both HIV and hepatitis B infection, your hepatitis B may get worse if you stop taking Delstrigo. You may need to have blood tests for several months after stopping treatment. Consult your doctor about your hepatitis B treatment.

Worsening of kidney problems, including kidney failure

These problems can affect some people taking Delstrigo. Your doctor will do blood tests to check your kidney function before and during treatment with Delstrigo.

Bone problems

These problems can affect some people taking Delstrigo. Tell your doctor if you have osteoporosis, have a history of bone fractures, or have bone problems. Bone problems (which can be felt as persistent or worsening bone pain and sometimes lead to fractures) can also occur due to damage to the kidney tubule cells (see section 4, Possible side effects). Tell your doctor if you have bone pain or fractures.

The use of tenofovir disoproxil can also cause bone loss. The greatest bone loss was seen in clinical studies where patients were treated with tenofovir disoproxil in combination with a boosted protease inhibitor.

In general, the effects of using tenofovir disoproxil on long-term bone health and the risk of future fractures in adults and pediatric patients are uncertain.

Immune reconstitution syndrome

This syndrome can occur when you start treatment with any HIV medicine, including Delstrigo. Your immune system may become stronger and start to fight infections that have been hidden in your body for a long time. Tell your doctor immediately if you start to have new symptoms after starting HIV medicine.

Autoimmune disorders (a condition where the immune system attacks healthy body tissue) can also occur after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders can occur many months after starting treatment. If you observe any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising towards the trunk of the body, palpitations, tremors, or hyperactivity, tell your doctor immediately to receive the necessary treatment.

Children and adolescents

Do not give this medicine to children under 12 years of age or weighing less than 35 kg. The use of Delstrigo in children under 12 years of age or weighing less than 35 kg has not been studied.

Other medicines and Delstrigo

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines. This is because other medicines may affect the way Delstrigo works, and Delstrigo may affect the way other medicines work.

There are some medicines that you should not take with Delstrigo. See the list in the section "Do not take Delstrigo".

Consult your doctor before taking the following medicines with Delstrigo, as your doctor may need to adjust the dose of your medicines:

• bosentan (a medicine to treat lung diseases)
• dabrafenib (a medicine to treat skin cancer)
• lesinurad (a medicine to treat gout)
• modafinil (a medicine to treat excessive sleepiness)
• nafcillin (a medicine to treat certain bacterial infections)
• rifabutin (a medicine to treat certain bacterial infections such as tuberculosis)
• telotristat ethyl (a medicine to treat diarrhea in people with carcinoid syndrome)
• thioridazine (a medicine to treat psychiatric disorders such as schizophrenia)

If your doctor decides that you should take these medicines with Delstrigo, your doctor will prescribe a 100 mg doravirine tablet to be taken daily, approximately 12 hours after the Delstrigo dose.

Your doctor may check your blood levels or monitor for side effects if you take the following medicines with Delstrigo:

• ledipasvir/sofosbuvir (medicines used to treat hepatitis C infection)
• sirolimus (a medicine used to control the immune response of your body after a transplant)
• sofosbuvir/velpatasvir (medicines used to treat hepatitis C infection)
• tacrolimus (a medicine used to control the immune response of your body after a transplant)
• medicines (usually liquids) that contain sorbitol and other sugar alcohols (such as xylitol, mannitol, lactitol, or maltitol), if taken regularly

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor about the risks and benefits of taking Delstrigo. It is recommended to avoid the use of Delstrigo during pregnancy. This is because Delstrigo has not been studied during pregnancy and it is not known whether Delstrigo will harm your baby while you are pregnant.

It is not recommended that HIV-infected women breastfeed their babies because HIV infection can be passed on to the baby through breast milk.

If you are breastfeeding or think you may want to breastfeed, consult your doctor as soon as possible.

Driving and using machines

Be careful when driving, cycling, or using machines if you feel tired, dizzy, or sleepy after taking this medicine.

Delstrigo tablets contain lactose

If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Delstrigo

Always take this medicine exactly as your doctor, pharmacist, or nurse has told you. If you are unsure, consult your doctor, pharmacist, or nurse. Delstrigo is a complete treatment in one tablet for the treatment of HIV infection.

How much to take

The recommended dose is one tablet once a day. If you are taking certain medicines, your doctor may need to adjust the amount of doravirine you take. See the section "Other medicines and Delstrigo" for the list of medicines.

How to take this medicine

• Swallow the tablet whole (do not crush or chew).
• This medicine can be taken with or without food.

If you take more Delstrigo than you should

Do not take a higher dose than recommended. If you accidentally take more than the prescribed dose, contact your doctor.

If you forget to take Delstrigo

• It is important that you do not miss or skip any dose of Delstrigo.
• If you forget to take a dose, take it as soon as you remember. However, if it is less than 12 hours until the time of your next dose, skip the missed dose and take the next dose at the usual time. Then continue with your treatment as usual.
• Do not take two doses of Delstrigo at the same time to make up for the missed dose.
• If you are unsure what to do, consult your doctor or pharmacist.

If you stop taking Delstrigo

Do not run out of Delstrigo. Refill your prescription or talk to your doctor before your Delstrigo supply runs out.

If you stop taking Delstrigo, your doctor will need to check your health frequently and do regular blood tests for several months to check your HIV infection. If you have HIV and hepatitis B, it is especially important that you do not stop Delstrigo without talking to your doctor first. Some patients have had blood test results or symptoms indicating that their hepatitis got worse after stopping treatment with lamivudine or tenofovir disoproxil (two of the three active substances in Delstrigo). If you stop Delstrigo, your doctor may recommend that you resume treatment for your hepatitis B. You may need to have blood tests to check your liver function for up to 4 months after stopping treatment. In some patients with advanced liver disease or cirrhosis, it is not recommended to stop treatment, as this can cause worsening of hepatitis that can be life-threatening.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Do not stop taking this medicine without talking to your doctor.

Stop taking Delstrigo and seek medical attention immediately if you notice any of the following symptoms: red patches on the trunk, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions can start with fever and symptoms similar to flu (Stevens-Johnson syndrome/toxic epidermal necrolysis). The frequency of these reactions cannot be estimated from the available data.

Other side effects that may occur

Common:may affect up to 1 in 10 people:

• abnormal dreams, difficulty sleeping (insomnia)
• headache, dizziness, drowsiness
• cough, nasal symptoms
• nausea, diarrhea, stomach pain, vomiting, gas (flatulence)
• hair loss, rash
• muscle symptoms (pain, stiffness)
• bone loss
• feeling tired, fever

Blood tests may also show:

• increased levels of liver enzymes (ALT)

Uncommon:may affect up to 1 in 100 people:

• nightmares, depression, anxiety, irritability, confusion, suicidal thoughts
• concentration problems, memory problems, tingling in hands and feet, muscle stiffness, poor quality sleep

• high blood pressure

• constipation, stomach upset, swelling or bloating of the stomach (abdominal distension), indigestion, soft stools, stomach spasms, frequent bowel movements, inflammation of the pancreas (pancreatitis) (causing stomach pain, vomiting)
• itching
• joint pain, muscle rupture, muscle weakness
• feeling weak, general feeling of being unwell

Blood tests may also show:

• decrease in white blood cell count (neutropenia)
• decrease in red blood cell count (anemia)
• decrease in platelet count (may bleed more easily)
• decrease in phosphate levels
• decrease in potassium levels in the blood
• increase in creatinine levels in the blood
• increase in liver enzymes (AST)
• increase in lipase levels
• increase in amylase levels
• decrease in hemoglobin levels

Muscle pain, muscle weakness, and decreased potassium or phosphate in the blood can occur due to damage to the kidney tubule cells.

Rare:may affect up to 1 in 1,000 people:

• aggression, hallucinations, difficulty adapting to changes, mood changes, sleepwalking

• difficulty breathing, swelling of the tonsils
• feeling of incomplete defecation

• enlarged liver or fatty liver, yellowing of the skin or eyes, abdominal pain caused by liver inflammation
• skin inflammation due to an allergy, redness of the cheeks, nose, chin, or forehead, bumps or pimples on the face, swelling of the face, lips, tongue, or throat
• muscle weakness, bone weakening (with bone pain and sometimes fractures)
• kidney damage, kidney stones, kidney failure, damage to the kidney tubule cells, kidney injury, excessive urine production, and feeling of thirst
• chest pain, feeling of cold, pain, thirst

Blood tests may also show:

• decrease in magnesium levels
• lactic acidosis (excess lactic acid in the blood)
• increase in creatine phosphokinase levels

Very rare:may affect up to 1 in 10,000 people:

Blood tests may also show:

• failure of the bone marrow to produce new red blood cells (pure red cell aplasia)

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Delstrigo

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the bottle after EXP.
• The bottle contains a desiccant that protects the tablets from moisture. There may be more than one in each bottle. Keep the desiccant in the bottle and do not throw it away until you have finished taking all the medicine.
• Keep the bottle tightly closed to protect it from moisture.
• This medicine does not require any special storage temperature.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Delstrigo Composition

• The active ingredients are 100 mg of doravirina, 300 mg of lamivudina, and 245 mg of tenofovir disoproxil (as fumarate)
• The other components are sodium croscarmellose E468; hypromellose acetate succinate; magnesium stearate E470b; microcrystalline cellulose E460; anhydrous colloidal silica E551; sodium stearyl fumarate. The tablets are coated with a film that contains the following components: carnauba wax E903; hypromellose E464; yellow iron oxide E172; lactose monohydrate; titanium dioxide E171 and triacetin E1518.

Product Appearance and Package Contents

Delstrigo is presented in film-coated tablets of yellow color, oval, engraved with the corporate logo and 776 on one side and smooth on the other side.

The following package sizes are available:

• 1 bottle with 30 film-coated tablets.
• 90 film-coated tablets (3 bottles of 30 film-coated tablets)

Only some package sizes may be marketed in your country.

Marketing Authorization Holder and Manufacturer

Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, Netherlands

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:{MM/AAAA}.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.